Proposed TOR File

FORM-1

FOR

PROPOSED PHARMA & PHARMA INTERMEDIATES MANUFACTURING UNIT

M/s. KESHAV INTERCHEM PLOT NO. 905/11/8, GIDC ESTATE, PANOLI-394 116, TALUKA: ANKLESHWAR, DISTRICT: BHARUCH, GUJARAT

Prepared by:

Aqua-Air Environmental Engineers Pvt. Ltd. (Pollution Control Consultants & Engineers)

Reg. Office: 403, Centre Point, Nr. Kadiwala School, Ring Road, Surat – 395 002, Gujarat, India Fax: +91 261 2707273 / 3987273 Tel: + 91 261 3048586 / 2460854 / 2461241 E-mail: [email protected] Visit us at: www.aqua-air.co.in

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APPENDIX I (See paragraph - 6) FORM 1 Sr. Item Details No. 1. Name of the project/s M/s. Keshav Interchem 2. S. No. in the schedule 5 (f) 3. Proposed capacity/area/length/tonnage Proposed Capacity = 15 MT/Month to be handled/command area/lease Total Plot Area = 2,767.18 m2 area/number of wells to be drilled 4. New/Expansion/Modernization New 5. Existing Capacity/Area etc. For detail Please refer Annexure – I 6. Category of Project i.e. ‘A’ or ‘B’ ‘B’ 7. Does it attract the general condition? If yes, please specify. 8. Does it attract the specific condition? If No yes, please specify. 9. Location Plot/Survey/Khasra No. Plot No. 905/11/8 Village GIDC estate, Panoli Tehsil Ankleshwar District Bharuch State Gujarat 10. Nearest railway station/airport along Railway Station: Ankleshwar (4.5 km) with distance in kms. Airport: Surat (60 km) 11. Nearest Town, city, District Panoli Village (3 km) Headquarters along with distance in Bharuch (15.5 km) kms. 12. Village Panchayats, Zilla Parishad, Notified Area Authority, Panoli Municipal Corporation, local body (complete postal address with telephone nos. to be given) 13. Name of the applicant M/s. Keshav Interchem 14. Registered Address Plot No. 905/11/8, GIDC estate, Panoli-394116, Taluka: Ankleshwar, District: Bharuch, Gujarat 15. Address for correspondence: Name Ms. Rutu Mahendrabhai Patel Designation (Owner/Partner/CEO) Proprietor Address M/s. Keshav Interchem

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A-1/32, Nirman complex, R. C. Technical Road, Chankyapuri, Ghatlodia, Ahmadabad- 386001 (Guj.) Pin Code 386001 E-mail [email protected] Telephone No. -- Fax No. -- Mobile No. +919429437733, +917203055448 16. Details of Alternative Sites examined, if NA any. Location of these sites should be shown on a topo sheet. 17. Interlinked Projects No 18. Whether separate application of No interlinked project has been submitted? 19. If yes, date of submission No 20. If no, reason No 21. Whether the proposal involves No approval/clearance under: if yes, details of the same and their status to be given. (a) The Forest (Conservation) Act, 1980? (b) The Wildlife (Protection) Act, 1972? (c) The C.R.Z. Notification, 1991? 22. Whether there is any Government No Order/Policy relevant/relating to the site? 23. Forest land involved (hectares) No 24. Whether there is any litigation pending No against the project and/or land in which the project is propose to be set up? (a) Name of the Court (b) Case No. (c) Orders/directions of the Court, if any and its relevance with the proposed project. • Capacity corresponding to sectoral activity (such as production capacity for manufacturing, mining lease area and production capacity for mineral production, area for mineral exploration, length for linear transport infrastructure, generation capacity for power generation etc.,)

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(II) Activity 1. Construction, operation or decommissioning of the Project involving actions, which will cause physical changes in the locality (topography, land use, changes in water bodies, etc.)

Sr. Information/Checklist confirmation Yes Details thereof with approximate No. /No quantities frates, wherever possible) with source of information data 1.1 Permanent or temporary change in No Proposed project activity is within land use, land cover or topography the Panoli GIDC Industrial Estate. including increase intensity of land use (with respect to local land use plan) 1.2 Clearance of existing land, Yes Minor site clearance activities shall vegetation and Buildings? be carried out to clear shrubs and weed. 1.3 Creation of new land u ses? No The project site is located on level ground, which does not require any major land filling for area grading work. 1.4 Pre-construction investigations e.g. No Proposed site is located within bore Houses, soil testing? earmarked industrial estate developed by GIDC. 1.5 Construction works? Yes Please refer Annexure – I. 1.6 Demolition works? No There will be not any demolition work at the site. 1.7 Temporary sites used for No Proposed site is located within construction works or housing of notified industrial estate developed construction workers? by GIDC and all required manpower will be employed from nearby area. 1.8 Above ground buildings, structures Yes Please refer Annexu re – I. or earthworks including linear structures, cut and fill or excavations 1.9 Underground works mining or No Not Required tunneling? 1.10 Reclamation works? No Not Required 1.11 Dredging? No Not Required 1.12 Off shore structures? No Not Required 1.13 Production and manufacturing Yes Please refer Ann exure – III. processes? 1.14 Facilities for storage of goods or Yes Areas for storage of raw materials materials? and finished products will be developed. 1.15 Facilities for treatment or disposal of Yes For Facilities for treat ment & solid waste or liquid effluents? disposal of liquid effluents please refer Annexure – V. For Hazardous waste details please refer Annexure – VII.

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1.16 Facilities for long term housing of No Not Concerned operational workers? 1.17 No There will be very minor traffic New road, rail or sea traffic during increase due to proposed project Construction or operation? and will not cause any change in locality. 1.18 No Proposed site is located within New road, rail, air waterborne or notified industrial estate having very other transport infrastructure well developed infrastructure including new or altered routes and facilities. Therefore, there will not be stations, ports, airports etc? any need of new transportation route/station. 1.19 Closure or diversion of existing No Not Applicable transport routes or infrastructure leading to changes in Traffic movements? 1.20 No Proposed site is situated in notified industrial estate having very well New or diverted transmission lines or developed transmission lines or pipelines for resources and effluent Pipelines? handling. Therefore, there will not be any need of new or diverted transmission lines or pipelines . 1.21 Impoundment, damming, culverting, No Water requir ed will be met through realignment or other changes to the GIDC Water Supply. hydrology of watercourses or aquifers? 1.22 Stream crossings? No Not Required 1.23 Abstraction or transfers of water Yes Water requirement will be met form ground or surface waters? through Panoli GIDC water supply. 1.24 Changes in water bodies or the land No Not Concerned surface affecting drainage or run -off? 1.25 Transport of personnel or materials Yes Transportation of personnel or raw for construction, operation or material and products will be decommissioning? primarily by road only. 1.26 Long-term dismantling or No Not Required decommissioning or restoration works? 1.27 Ongoing activity during No Not Concerned decommissioning which could have an impact on the environment? 1.28 Influx of people to an area either Yes Direct/Indirect employment shall be temporarily or permanentl y? provided for proposed operation. 1.29 Introduction of alien species? No Not Concerned 1.30 Loss of native species or genetic No Not Concerned diversity? 1.31 Any other actions? No Not Concerned

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2. Use of Natural resources for construction or operation of the Project (such as land, water, materials or energy, especially any resources which are non-renewable or in short supply):

Sr. Information/checklist confirmation Yes/ Details thereof (with approximate No. No quantities /rates, wherever possible) with source of information data 2.1 Land especially undeveloped or No Proposed project activity will be agricultural land (ha) within GIDC Industrial Area, Panoli, District: Bharuch, Gujarat. 2.2 Water (expected source & competing Yes Water Source: Panoli GIDC Water users) unit: KLD Supply. For details please refer Annexure – IV. 2.3 Minerals (MT) No Not Required 2.4 Construction material – stone, Yes Construction materials, like steel, aggregates, and / soil cement, crushed stones, sand, (expected source – MT) rubble, etc. required for the project shall be procured from the local market of the region. 2.5 Forests and timber (source – MT) No Not Required 2.6 Energy including electricity and fuels Yes Power required will be 400 KVA (source, competing users) Unit: fuel Source: DGVCL (MT), energy (MW) Note: DG Set 100 KVA will be kept for emergency power back up. Fuel Requirement: Natural Gas = 500 SM 3/Day Diesel = 50 Liter/Day 2.7 Any other natural resources No Not Required (use appropriate standard units)

3. Use, storage, transport, handling or production of substances or materials, which could be harmful to human health or the environment or raise concerns about actual or perceived risks to human health.

Sr. Information/Checklist confirmation Yes/ Details there of (with approximate No. No quantities/rates, wherever possible) with source of information data 3.1 Use of substances or materials, which Yes Please refer Annexure – VIII. are hazardous (as per MSIHC rules) to human health or the environment (flora, fauna, and water supplies) 3.2 Changes in occurrence of disease or No Not Required affect disease vectors (e.g. insect or water borne diseases) 3.3 Affect the welfare of people e.g. by No The project will bring direct / indirect changing living conditions? employment opportunity, which will Page 6 of 179

enhance the socio-economic status of the area. 3.4 Vulnerable groups of people who No Proposed site is located within could be affected by the project e.g. notified industrial estate developed hospital patients, children, the by GIDC. elderly etc. 3.5 Any other causes No Not Required

4. Production of solid wastes during construction or operation or decommissioning (MT/month)

Sr. Information/Checklist confirmation Yes/ Details there of (with approximate No. No quantities/rates, wherever possible) with source of information data 4.1 Spoil, overburden or mine wastes No Not Applicable 4.2 Municipal waste (domestic and or Yes Through Septik Tank / Soak Pit commercial wastes) 4.3 Hazardous wastes (as per Hazardous Yes Please refer Annexure – VII. Waste Management Rules) 4.4 Other industrial process wastes Yes Please refer Annexure – VI I. 4.5 Surplus product There will not be any surplus No product. 4.6 Sewage sludge or other sludge from Please refer Annexure – VII. Yes effluent treatment 4.7 Construction or demolition wastes Construction waste shall be utilized Yes for leveling, land filling in the premises. 4.8 Redundant machinery or equipment All machinery / equipment will be No installed as per requirement. 4.9 Contaminated soils or other No Not Concerned materials 4.10 Agricultural wastes No Not Concerned 4.11 Other solid wastes Yes Please refer Annexure – VII.

5. Release of pollutants or any hazardous, toxic or noxious substances to air (Kg/hr)

Sr. Information/Checklist confirmation Yes/ Details there of (with approximate No. No quantities/rates, wherever possible) with source of information data 5.1 Emissions from combustion of fossil Yes Please refer Annexure – VI. fuels from stationary or mobile sources 5.2 Emissions from production processes Yes Please refer Annexure – VI. 5.3 Emissions from materials handling Yes Solid raw materials shall be charged storage or transport through close pipeline into reactors Page 7 of 179

and the dust collection hopper shall be connected to a bag filter and ID fan. 5.4 Emissions from construction Yes During construction work, only dust activities including plant and contamination will be there & water equipment sprinklers shall be utilized whenever necessary. 5.5 Dust or odours from handling of No Dust from drying will be collected in materials including construction to dust collector through cyclone materials, sewage and waste separator & recovered powder will be recycled back to process. Air Handling Unit will be provided where ever applicable. 5.6 Emissions from incineration of waste There will not be incineration of No waste. 5.7 Emissions from burning of waste in No No open burning will be carried out open air e.g. slash materials, within premises. construction debris) 5.8 Emissions from any other sources Yes Please refer Annexure – VI.

6. Generation of Noise and Vibration, and Emissions of Light and Heat:

Sr. Information/Checklist confirmation Yes/ Details there of (with approximate No. No quantities/rates, wherever possible) with source of information data with source of information data 6.1 From operation of equipment e.g. Yes The Noise level will be within the engines, ventilation plant, crushers prescribed limit. At noisy areas adequate preventive & control measures will be taken. No significant noise, vibration or emission of light & heat from the unit. 6.2 From industrial or similar processes Yes All machinery / equipment shall be well maintained, shall be proper foundation with anti vibrating pads wherever applicable and noise levels within permissible limits. 6.3 From construction or demolition No AcousticMinor noi enclosuresse will be shall generated be provided during construction work. 6.4 From blasting or piling No No blasting or pilling will be carried out at project site. 6.5 From construction or operational No Not Concerned traffic 6.6 From lighting or cooling systems No Not Concerned

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6.7 From any other sources No Not Concerned

7. Risks of contamination of land or water from releases of pollutants into the ground or into sewers, surface waters, groundwater, coastal waters or the sea:

Sr. Information/Checklist confirmation Yes/ Details there of (with approximate No. No quantities/rates, wherever possible) with source of information data 7.1 From handling, storage, use or Yes Please refer Annexure – VIII. spillage of hazardous materials 7.2 From discharge of sewage or other Yes Sewage shall be treated in Septic effluents to water or the land Tank / Soak Pit. (expected mode and place of For details please refer Annexure – V. discharge) 7.3 By deposition of pollutants emitted No Not Concerned to air into the and or into water 7.4 From any other sources No Not Concerned 7.5 Is there a risk of long term build up of No Not Concerned pollutants in the environment from these sources?

8. Risk of accidents during construction or operation of the Project, which could affect human health or the environment

Sr. Information/Checklist confirmation Yes/ Details there of (with approximate No. No quantities/rates, wherever possible) with source of information data

8.1 From explosions, spillages, fires etc Yes Please refer Annexure – VIII. from storage, handling, use or production of hazardous substances 8.2 From any other causes No Not Concerned 8.3 Could the project be affected by No Not Concerned natural disasters causing environmental damage (e.g. floods, earthquakes, landslides, cloudburst etc)?

9. Factors which should be considered (such as consequential development) which could lead to environmental effects or the potential for cumulative impacts with other existing or planned activities in the locality

Sr. Information/Checklist confirmation Yes/ Details there of (with approximate No. No quantities/rates, wherever possible) with source of information data 9.1 Lead to development of supporting. Yes Please refer Annexure – IX. utilities, ancillary development or development stimulated by the project which could have impact on Page 9 of 179

the environment e.g. • Supporting infrastructure (roads, power supply, waste or waste water treatment, etc.) • housing development • extractive industry • supply industry • other 9.2 Lead to after-use of the site, which No Not Concerned could have an impact on the environment 9.3 Set a precedent for later No Not Concerned developments 9.4 Have cumulative effects due to No Not Concerned proximity to other existing or planned projects with similar effects

(III) Environmental Sensitivity

Sr. Areas Name/ Aerial distance (within 5 km) No. Identity Proposed project location boundary 1 Areas protected under international No No protected area within 5 km from conventions, national or local the proposed project site. legislation for their ecological, landscape, cultural or other related value 2 Areas which important for are or Yes River Narmada = 11 km sensitive Ecol logical reasons - Wetlands, watercourses or other water bodies, coastal zone, biospheres, mountains, forests 3 Area used by protected, important or No Not Concerned sensitive Species of flora or fauna for breeding, nesting, foraging, resting, over wintering, migration 4 Inland, coastal, marine or No Not Concerned underground waters 5 State, National boundaries No No state or national boundary falls within 5 km aerial distance from the project site. 6 Routes or facilities used by the public Yes Public transportation for access to recreation or other tourist, pilgrim areas. 7 Defense installations Yes Ankleshwar 8 Densely populated or built-up area Yes Panoli village 3 km and Ankleshwar City around 4.5 km from the propose d project site .

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9 Area occupied by sensitive man-made No Not Applicable land uses Hospitals, schools, places of worship, community facilities) 10 Areas containing important, high No Not Concerned quality or scarce resources (ground water resources, surface resources, forestry, agriculture, fisheries, tourism, minerals) 11 Areas already subjected to pollution Yes Ankleshwar environmental damage. (those where existing legal environmental standards are exceeded) 12 Areas susceptible to natural hazard No Not Applicable which could cause the project to present environmental problems (earthquakes, subsidence, landslides, flooding erosion, or extreme or adverse climatic conditions)

IV). Proposed Terms of Reference for EIA studies: Please refer Annexure - X

I hereby given undertaking that, the data and information given in the application and enclosures are true to the best of my knowledge and belief and I am aware that if any part of the data and information submitted is found to be false or misleading at any stage the project will be rejected and clearance give, if any to the project will be revoked at our risk and cost.

Date: October 30, 2017 Place: GIDC, Panoli FOR KESHAV INTERCHEM

MS. RUTU MAHENDRABHAI PATEL (PROPRIETOR)

NOTE:

1. The projects involving clearance under Coastal Regulation Zone Notification, 1991 shall submit with the application a C.R.Z. map duly demarcated by one of the authorized agencies, showing the project activities, w.r.t. C.R.Z. (at the stage of TOR) and the recommendations of the State Coastal Zone Management Authority (at the stage of EC). Simultaneous action shall also be taken to obtain the requisite clearance under the provisions of the C.R.Z. Notification, 1991 for the activities to be located in the CRZ. 2. The projects to be located within 10 km of the National Parks, Sanctuaries, Biosphere Reserves, Migratory Corridors of Wild Animals, the project proponent shall submit the map duly authenticated by Chief Wildlife Warden showing these features vis-à-vis the project

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location and the recommendations or comments of the Chief Wildlife Warden thereon (at the stage of EC). 3. All correspondence with the Ministry of Environment & Forests including submission of application for TOR/Environmental Clearance, subsequent clarifications, as may be required from time to time, participation in the EAC Meeting on behalf of the project proponent shall be made by the authorized signatory only. The authorized signatory should also submit a document in support of his claim of being an authorized signatory for the specific project.

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LIST OF ANNEXURES

SR. NO. NAME OF ANNEXURE I Layout Map of the Plant II List of Products and Raw materials along with their Production Capacity III Brief Manufacturing Process Description IV Details of water consumption & waste water generation V Details of Effluent Treatment Scheme VI Details of Air Pollution Control System VII Details of Hazardous Waste Generation and Disposal VIII Details of Hazardous Chemicals Storage & Handling IX Socio-economic Impacts X Proposed Terms of Reference XI Copy of Plot Allotment Letter XII Copy of GIDC Water Supply Certificate XIII Membership Certificate of CETP (M/s. PETL) XIV Membership Certificate of Common Solid Waste Disposal Facility & Common Incineration Facility (M/s. BEIL) XV Toposheet

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ANNEXURE - I ______LAYOUT OF MAP OF THE PLANT

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ANNEXURE - II ______LIST OF PRODUCTS ALONG WITH THEIR PRODUCTION CAPACITY

SR. QUANTITY END USE PRODUCT NAME CAS NO. NO. MT / MONTH Group – I 1 Phenylephrine hcl AND/OR 61-76-7 Pharma 2 Ofloxacin AND/OR 82419-36-1 Pharma 3 Olanzapine AND/OR 132539-06- Pharma 1

4 Hydrochlorothiazide AND/OR 58-93-5 Pharma

5 Oxcarbazepine AND/OR 28721-07-5 Pharma 6 10-Methoxy-5H-dibenz[b,f]azepine-5- 28721-08-6 Pharma carbonylchloride, 10- Methoxyiminostilbene-5-carbonylchloride AND/OR

7 Diclofenac sodium AND/OR 15307-79-6 Pharma

8 2,6 – dichloro diphenyl amine (dcdpa) 15307-93-4 Pharma AND/OR 9 N-chloroacetyl-n-phenyl-2,6-dichloro 15308-01-7 Pharma aniline (cpdca) AND/OR

10 Indolenone [ (n-1) of dicofenac ] AND/OR 15362-40-0 Pharma

11 2-Hydroxymethyl-3-methyl-4-(3-methoxy 153259-31- 7.0 Pharma propanoxyl)pyridine HCL AND/OR 5 12 1,2-benisoxazole-3-acetica acid AND/OR 37924-67-7 Pharma 13 Cis-tosylate AND/OR 134071-44- Pharma 6 14 Atorvastatin calcium AND/OR 134523-03- Pharma 8 15 tert-Butyl (4R,6R)-2-[[[6-(2-4-fluorophenyl)- 65564-05-8 Pharma 5-isopropyl-3-phenyl-4- (phenylcarbamoyl)pyrrol-1-yl]ethyl]-2,2- dimethyl-1,3-dioxan-4-yl]acetate AND/OR 16 Nebivolol Hydrochloride AND/OR 152520-56- Pharma 4 17 Pantaprazol Sodium AND/OR 138786-67- Pharma 1 18 5-(Difluoromethoxy)-2- {[( 102625-64- Pharma 3,4Dimethoxypyridin - 2-yl) methyl]thio}- 9 1H-benzimidazolee AND/OR Page 15 of 179

SR. QUANTITY END USE PRODUCT NAME CAS NO. NO. MT / MONTH 19 N-((4-Chloromethyl)-2-Thiozolyl)Guanidine 84545-70-0 Pharma Hydrochloride AND/OR 20 Methyl 3-amino-2 butenoate AND/OR 14205-39-1 Pharma 21 2,4-Difluoro-2-(1h- 1,2,4-Triazole-1-Yl) 86404-63-9 Pharma Acetophenone (Dfta) AND/OR 22 cis-2-(2,4-Dichlorophenyl)-2-(1H-1,2,4- 67914-86-7 Pharma triazol-1-ylmethyl)-1,3-dioxolan-4-ylmethyl methane sulphonate AND/OR 23 1-(4-Methoxyphenyl)-1-(4-nitrophenyl) 74852-61-2 Pharma piperazine AND/OR 24 2-[[4-(2-Methoxyethyl)phenoxy]methyl- 56718-70-8 Pharma oxirane AND/OR 25 3''-acetyl-2''-hydroxy-4-(4 phenylbutoxy) 136450-06- Pharma benzanilide AND/OR 1 Group – II 26 Prasugrel Hydrochloride AND/OR 389574-19- Pharma 0 27 5-[2-Cyclopropyl-1-(2-fluorophenyl)-2- 150322-38- Pharma oxoethyl] -5,6,7,7a-tetrahydrothieno[3,2- 6

c]pyridin-2(4H)-one AND/OR

28 Dabigatran AND/OR 211915-06- Pharma 9 29 Femotidine AND/OR 76824-35-6 Pharma 30 N-[(2'-Cyano[1,1'-biphenyl]-4-yl)methyl]-L 137863-89- Pharma valine methyl ester AND/OR 9

31 Amlodipin besylate AND/OR 111470-99- Pharma 5.0 6 32 Amlodipine base AND/OR 88150-42-9 Pharma 33 2,4-dihydro-4-[(4-(4-hydroxyphenyl)-1- 106461-41- Pharma piperazinyl)phenyl]-2-(1-methylpropyl)-3h- 0 1,2,4-triazole-3-one AND/OR 34 Metoprolol tartrate AND/OR 56392-17-7 Pharma 35 1-(Isopropylamino)-3-[4-(2-methoxyethyl) 37350-58-6 Pharma phenoxy]-2-propanol AND/OR 36 Metoprolol succinate AND/OR 98418-47-4 Pharma 37 Ketoconazole AND/OR 65277-42-1 Pharma 38 Phthaloyl amlodipine AND/OR 88150-62-3 Pharma 39 2,4-Dihydro-4-[4-[4-(4-methoxyphenyl)-1- 252964-68- Pharma piperazinyl]phenyl]-2-(1-methylpropyl)-3H- 4 Page 16 of 179

SR. QUANTITY END USE PRODUCT NAME CAS NO. NO. MT / MONTH 1,2,4-triazol-3-one AND/OR Group – III 40 Montelukast sodium AND/OR 151767-02- Pharma 1 41 Valsartan AND/OR 137862-53- Pharma 4 3.0 42 Venlafaxine Hydrochloride AND/OR 99300-78-4 Pharma 43 Levocetirizine Dihydrochloride AND/OR 130018-77- Pharma 8 44 Pregabalin AND/OR 148553-50- Pharma 8 45 Veratric Acid AND/OR 93-07-2 Pharma 46 Fluconazole AND/OR 86386-73-4 Pharma 47 Itraconazole AND/OR 84625-61-6 Pharma 48 Cetirizine Dihydrochloride AND/OR 83881-51-0 Pharma 49 Rabeprazole sodium AND/OR 117976-90- Pharma 6 50 Pranlukast AND/OR 103177-37- Pharma 3 51 Zonisamide AND/OR 68291-97-4 Pharma 52 Telmisartan AND/OR 144701-48- Pharma 4 53 Rosuvastatine calcium AND/OR 147098-20- Pharma 2 54 Posaconazole AND/OR 1712228- Pharma 49-2 55 Ursodiol AND/OR 128-13-2 Pharma TOTAL QUANTITY PRODUCTION PER MONTH 15

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LIST OF RAW MATERIAL

Product Name Raw Material Name KG/KG KG/MONTH Group – I Phenylephrine hcl isopropyl alcohol Hcl 0.92 1840.00 Ranney nickel (10% 0.12 240.00 charcoal) Anhydrous aluminum 0.06 120.00 chloride Ethyl acetate 2.33 4660.00 Hydrochloric acid 0.29 580.00 Hydrogen gas 0.01 20.00 Hyflowsuper cell 0.01 20.00 Isopropyl alcohol 14.17 28340.00 Liquid bromine 0.68 1360.00 Methanol 8.33 16 660.00 M-hydroxy acetophenone 1.17 2340.00 N-methyl benzyl amine 0.86 1720.00 Toluene 2.33 4660.00 Ofloxacin Quinolic Acid 1.25 2500.00 N-methyl Piperazine 0.90 1800.00 Butanol 1.00 2000.00 Acetic Acid 0.30 600.00 Liquid Ammonia 0.45 90 0.00 Olanzapine Methyl piperazinyl 1.07 2140.00 4-chloro 2-methyl 10h- 1.33 2660.00 thieno [2,3b][1,5] benzodiazepine N N Dimethyl amine 5.33 10660.00 Acetonitrile 4.00 8000.00 Hydrochlorothiazide 5-Chloro Aniline 2-4 1.20 2400.00 Disulfonamide Sulphuric acid 0.16 320.00 Methanol 0.39 780.00 Formaldehyde 0.10 200.00 Sodium hydroxide 0.05 100.00 Hydrochloric acid 0.14 280.00 Activated carbon 0.01 20.00 Oxcarbazepine 5H-Dibenz [b,f]azepine-5- 1.35 2700.00 carbonitrile Sodium nitrite 0.68 1360.00 Acetic acid 1.95 3900.00 Iron 0.08 160.00 Boron TriFluoride 0.35 700.00 IsoPropylAmine 2.25 4500.00 10-Methoxy-5H- 5H-Dibenz [b,f]azepine-5- 2460.00 dibenz[b,f]azepine -5- carbonitril e 1.23 Page 18 of 179

carbonylchloride, 10- Sodium nitrite 0.62 1240.00 Methoxyiminostilbene-5- Acetic acid 3400.00 carbonylchloride 1.70 Diclofenac sodium 2,6 Dichlorophenol 0.62 1240.00 Sodium Methoxide 1.46 2920.00 soln.25% Ethyl Chloro Acetate 0.44 880.00 Aniline 0.34 680.00 Caustic Lye 0.22 440.00 Chloro Acetyl Chloride 0.58 1160.00 Ethoxy ethanol 2.20 4400.00 Aluminum Chloride 0.66 1320.00 Sodium Hydroxide 0.30 600.00 Activated Carbon 0.01 20.00 2,6 – dichloro diphenyl amine 2,6 Dichlorophenol 0.77 1540.00 (dcdpa) Sodium Methoxide sol n.25% 1.82 3640.00 Ethyl Chloro Acetate 0.55 1100.00 Aniline 0.42 840.00 Caustic Lye 0.28 560.00 N-chloroacetyl-n-phenyl-2,6- 2,6 Dichlorophenol 0.62 1240.00 dichloro aniline (cpdca) Sodium Methoxide soln.25% 1.46 2920.00 Ethyl Chloro Acetate 0.4 4 880.00 Aniline 0.34 680.00 Caustic Lye 0.22 440.00 Chloro Acetyl Chloride 0.58 1160.00 Ethoxy ethanol 2.20 4400.00 Indolenone 2,6 Dichlorophenol 0.62 1240.00 Sodium Methoxide soln.25% 1.45 2900.00 Ethyl Chloro Acetate 0.43 860.00 Aniline 0.33 660.00 Caustic Lye 0.22 440.00 Chloro Acetyl Chloride 0.58 1160.00 Ethoxy ethanol 2.20 4400.00 Aluminium Chloride 0.66 1320.00 2-Hydroxymethyl-3-methyl-4- 2,3 Lutidine 0.51 255.00 (3-methoxy Acetic acid 0.51 255.00 propanoxyl)pyridine HCL Hydrogen peroxide 0.37 185.00 Nitric acid 0.33 165.00 Sulfuric acid 1.2 600.00 3-Methoxy-1-propanol 0.44 220.00 Acetic anhydride Sodium hydroxide 0.42 210.00 Toluene 10.55 5275.00 Dimethyl Sulphoxide 2.22 1110.00 Acetic anhydride 1.67 835.00 Hydrochloric acid 0.22 110.00

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1,2-benisoxazole-3-acetica acid Methanol 0.72 360.00 4Hydroxy Coumarin 0.92 460.00 Hydroxylamine hydrochloride 1.37 685.00 Potassium acetate 1.93 965.00 Sodium hydroxide 0.09 45.00 Methylene Dichloride 2.29 1145.00 Hydrochloric Acid 0.47 235.00 Cis-tosylate Cis -BromoBenzoate 1.30 3250.00 Imidazole 1.16 2900.00 Dimethylformemide(DMF) 0.06 150.00 Toluene 3.80 9500.00 Sodium Bicarbonate 0.25 625.00 Sodium hydroxide 0.20 500.00 Hydro chloric acid 0.28 700.00 Ethyl Acetate 2.85 7125.00 Activated Carbon 0.01 25.00 Vacuum Salt 0.01 25.00 Methylene chloride 5.36 13400.00 P-Toluene Sulfonyl Chloride 0.78 1950.00 Sodium Carbonate 0.52 1300.00 Methanol 2.37 5925.00 Atorvastatin calcium (2R-trans)-5-(4- 1.91 4775.00 Fluorophenyl)-2-(1- Methyl)-N,4diphenyl-1-[2- Tetra hydroxy-4-hydroxy- 6-Oxo-2H-pyran-2yl)ethyl]- 1H-pyrrole-3-carboxamide Isopropyl Amine 3.98 9950.00 Sodium Hydroxide 0.31 775.00 Calcium Acetate solution 1.40 3500.00 tert-Butyl (4R,6R)-2-[[[6-(2-4- (2R-trans)-5-(4- Fluorophenyl) 1.90 4750.00 fluorophenyl)-5-isopropyl-3- 2-(1- phenyl-4- Methyl)-N,4diphenyl-1-[2- (phenylcarbamoyl)pyrrol-1- Tetra yl]ethyl]-2,2-dimethyl-1,3- hydroxy-4-hydroxy- 6-Oxo-2H dioxan-4-yl]acetate pyran-2- yl)ethyl]- 1H-pyrrole-3- carboxamide Iso Propyl Alcohol 2.23 5575.00 Sodium Hydroxide 0.31 775.00 Calcium Acetate solution 1.39 3475.00 Nebivolol Hydrochloride Benzopyran-2- 1.40 3500.00 Carboxaldehyde Derivative Trimethylsulfoxonium 1.15 2875.00 iodide Potassium hydroxide 0.56 1400.00 Benzyl amine 0.40 1000.00 Page 20 of 179

Toluene 3.00 7500.00 Ammonium formate 0.60 1500.00 Hydrogen gas 0.01 25.00 Methanol 5.20 13000.00 Pantaprazol Sodium 10% Sodium Hypochlorite 2.79 6975.00 Acetone 6.23 15575.00 Diflouro methoxy -2-MB 0.73 1825.00 Iso Propyl Acetate 11.54 28850.00 Sodium Hydroxide 0.41 1025.00 Pantoprazole chloro 0.77 1925.00 compound Pantoprazole sulfide 1.15 2875.00 5-(Difluoromethoxy)-2- {[( Pantoprazole chloro compound0.67 1675.00 3,4Dimethoxypyridin - 2-yl) Diflouro Methoxy -2-MB 0.64 1600.00 methyl]thio}-1H- Sodium Hydroxide 0.26 650.00 benzimidazolee Iso propyl alcohol 4.02 10050.00 N-((4-Chloromethyl)-2- 1,3 -Dichloro acetone 0.63 1575 .00 Thiozolyl)Guanidine Guanylthiourea 0.56 1400.00 Hydrochloride Potassium Iodide 0.02 50.00 Acetone 1.91 4775.00 Methyl 3-amino-2 butenoate Methyl aceto acetate 1.14 3990.00 Liq ammonia 2.75 9625.00 2,4-Difluoro-2-(1h- 1,2,4- 1,3 -Difluorobenzen e 0.55 1925.00 Triazole-1-Yl) Acetophenone Aluminium Chloride 0.65 2275.00 (Dfta) Methylene Chloride 3.25 11375.00 Chloroacetyl chloride 0.57 1995.00 4-Amino -1,2,4 -Triazole 0.44 1540.00 Iso Propyl Alcohol 2.14 7490.00 Hydrochloric acid 0.20 700.00 Sodium Nitrite 0.32 1120.00 Hydrochloric acid 0.68 2380.00 Ammonia Solution 0.55 1925.00 Sodium bicarbonate 0.04 140.00 cis-2-(2,4-Dichlorophenyl)-2- Cis -Bromobenzoate 1.10 3850.00 (1H-1,2,4-triazol-1-ylmethyl)- 1H,1,2,4 -Triazole 0.70 2450.00 1,3-dioxolan-4-ylmethyl Potassium carbonate 1.05 3675.00 methane sulphonate Dimethyl formamide 1.85 6475.00 Sodium hydroxide 0.17 595.00 Toluene 1.56 5460.00 Triethyl amine 0.40 1400.00 Methane sulfonyl chloride 0.38 1330.00 Methylene chloride 1.92 6720.00 Activated Carbon 0.04 140.00 1-(4-Methoxyphenyl)-4-(4- 1-(4 -Methyxy) piperadine 0.66 2310.00 nitrophenyl) piperazine Paranitrochlorobenzene 0.54 1890.00 Potassium carbonate 0.58 2030.00

Page 21 of 179

Dimethyl formamide 0.76 2660.00 Methanol 1.53 5355.00 Acetone 1.55 5425.00 Carbon 0.01 35.00 2-[[4-(2- 4- (2 - Methoxyethyl) 2800.00 Methoxyethyl)phenoxy]methyl- Phenol 0.80 oxirane Epichlorohydrine 0.80 2800.00 Sodium hydroxide 0.24 840.00 3''-acetyl-2''-hydroxy-4-(4 4-(4-phenylbutoxy)benzoic acid0.80 2800.00 phenylbutoxy) benzanilide 1-(3-amino-2-hydroxyphenyl) 0.46 1610.00 Ethanone Methylene Dichloride(F/R) 4.70 16450.00 Dimethyl Formamide 0.04 140.00 Thionyl Chloride 0.47 1645.00 Pyridine 0.71 2485.00 Hydrochloric acid 2.40 8400.00 Sodium Bicarbonate 0.24 840. 00 Prasugrel Hydrochloride 2-Bromo-1-cyclopropyl-2- 0.88 2200.00 (2 flourophenyl)ethanone 5,6,7,7a-tetrahydrothieno 0.54 1350.00 [3,2 -c]pyridine -2-(4H) -one Potassium Hydroxide 0.22 550.00 Methanol 8.76 21900.00 Acetic anhydride 0.32 800.00 Methyl ethyl ketone 2.94 7350.00 Hydrochloric Acid 0.10 250.00 Acetone 3.12 7800.00 5-[2-Cyclopropyl-1-(2- 2-Bromo-1-cyclopropyl-2-(2- 0.90 2250.00 fluorophenyl)-2-oxoethyl] - flourophenyl)ethanone 5,6,7,7a-tetrahydrothieno[3,2- 5,6,7,7a-tetrahydrothieno[3,2 0.55 1375.00 c]pyridin-2(4H)-one c]pyridine -2-(4H) -one Potassium Hydroxide 0.23 575.00 Methanol 2.70 6750.00 Dabigatran 3-[(1-Methyl-2-{[4-(5-oxo- 0.97 2425.00 4,5-dihydro- [1,2,4]oxadiazol-3-yl)- phenylamino]-methyl)-1H benzoimidazole- 5carbonyl)-pyridin-2- ylamino]- propionic acid ethyl ester P-toluene sulphonic acid 0.25 625.00 Acetic acid 0.20 500.00 Ethanol 25.00 62500.00 Hexachloroformate 0.28 700.00 Acetone 12.00 30000.00 Potassium Hydroxide 0.09 225.00 Page 22 of 179

Hydrochloric acid 0.00 20.00 Femotidine 1,3-Dichloro acetone 0.53 1325.00 Guanylthiourea 0.50 1250.00 Potassium Iodide 0.02 50.00 Acetone 1.70 4250.00 Thiurea 0.25 625.00 Sodium Hydroxide 0.40 1000.00 N-Sulfamyl-3-chloro 0.74 1850.00 propionamidineHCl Acetic acid 0.25 625.00 Methanol 34.36 85900.00 Ammonia (23%) 0.24 600.00 Activated carbon 0.06 150.00 N-[(2'-Cyano[1,1'-biphenyl]-4- L-Valine 0.50 1250.00 yl)methyl]-L valine methyl ester Thionyl Chloride 0.50 1250.00 Methanol 8.89 22225.00 Toluene 12.22 30550. 00 4-Bromomethyl -biphenyl -2- 2275.00 carbonitrile 0.91 Potassium carbonate 0.50 1250.00 Amlodipinbesylate Acetic Acid 0.43 1505.00 Benzene Sulfonic Acid 0.64 2240.00 Ethyl acetate 0.14 490.00 Ethyl Chloroaceto acetate 0.55 1925.00 Hydrochlo ric Acid 0.05 175.00 Haxene 0.22 770.00 Liq. Ammonia 0.96 3360.00 Methanol 0.05 175.00 Methyl aceto acetate 0.50 1750.00 Mono Methyl Amine 3.75 13125.00 Monoethanol amine 0.45 1575.00 Ortho Chlorobenzaldehyde 0.40 1400.00 Phthalic anhyd ride 1.00 3500.00 Piperidine 0.02 70.00 Sodium chloride 0.50 1750.00 Sodium hydride 0.28 980.00 Toluene 0.23 805.00 Amlodipine base Phthalic anhydride 1.00 3500.00 Mono ethanol amine 0.45 1575.00 Toluene 9.11 31885.00 Methyl aceto acetat e 0.40 1400.00 Liq ammonia 0.96 3360.00 Ethyl Chloroaceto acetate 0.55 1925.00 Hydrochloric Acid 0.05 175.00 Acetic acid 0.43 1505.00 Sodium chloride 0.50 1750.00 Sodium hydride 0.28 980.00 Page 23 of 179

Ortho Chlorobenzaldehyde 0.40 1400.00 Hexane 1.91 6685.00 Piperidine 0.02 70.00 Ethyl acetate 35.0 122500.00 Hexane 35.6 124600.00 Mono Methyl Amine 37.5 131250.00 2,4-dihydro-4-[(4-(4- 1-(4 -Methyxy) piperadine 1.12 39 20.00 hydroxyphenyl)-1- Paranitrochlorobenzene 0.92 3220.00 piperazinyl)phenyl]-2-(1- Potassium carbonate 1.64 5740.00 methylpropyl)-3h-1,2,4-triazole- Dimethyl formamide 13.93 48755.00 3-one Methanol 2.60 9100.00 Acetone 2.63 9205.00 Carbon 0.02 70.00 Palladium carbon 0.01 35.00 Hydrogen gas 0.13 455.00 Phenyl chlorofo rmate 1.01 3535.00 Sodium bicarbonate 0.91 3185.00 Methylene chloride 3.15 11025.00 Hydragin hydrate 0.84 2940.00 n-Butanol 1.88 6580.00 Formamidine acetate 0.82 2870.00 2-Bromo butane 1.60 5600.00 Hydrochloric acid 0.49 1715.00 Hydrobromic acid 12.32 43120.00 Sodium carbonate 1.12 3920.00 Metoprolol tartrate 4- (2- Methoxyethyl) 0.89 3115.00 Phenol Epichlorohydrine 0.89 3115.00 Sodium hydroxide 0.27 945.00 Mono isopropyl amine 2.68 9380.00 Toluene 3.57 12495.00 Hydrochloric Acid 0.54 1890.00 Caustic lye 0.27 945.00 Ethyl Acetate 3.57 12495.00 Tartaric Acid 0.24 840.00 Methanol 0.63 2205.00 1-(Isopropylamino)-3-[4-(2- 4- (2 - Methoxyethyl) 2345.00 methoxyethyl) phenoxy]-2- Phenol 0.67 propanol Epichlorohydrine 0.67 2345.00 Sodium Hydroxide 0.20 700.00 Mono isopropyl amine 2.02 7070.00 Toluene 2.69 9415.00 Hydrochloric acid 0.40 1400.00 Caustic lye 0.20 700.00 Metoprolol succinate 4- (2 -Methoxyethyl) Phenol 0.89 3115.00 Epichlorohydrine 0.89 3115.00 Sodi um hydroxide 0.27 945.00 Page 24 of 179

Mono isopropyl amine 2.68 9380.00 Toluene 3.57 12495.00 Hydrochloric Acid 0.54 1890.00 Caustic lye 0.27 945.00 Ethyl Acetate 3.57 12495.00 Succinic Acid 0.19 665.00 Methanol 0.63 2205.00 Ketoconazole Cis -BromoBe nzoate 1.53 3825.00 Imidazole 1.36 3400.00 Dimethylformemide(DMF) 0.07 175.00 Toluene 4.46 11150.00 Sodium Bicarbonate 0.29 725.00 Sodium hydroxide 0.90 2250.00 Hydrochloric Acid 0.31 775.00 Ethyl Acetate 7.70 19250.00 Vacuum Salt 0.01 25.00 PeraHydroxy phenyl n- 0.56 1400.00 acetyl piperazine Dimethyl Sulfoxide 1.66 4150.00 Sodium methoxide powder 0.14 350.00 Acetone 0.67 1675.00 Methanol 0.92 2300.00 Activated Carbon 0.05 125.00 Phthaloyl amlodipine Phthalic anhydride 0.67 2345.00 Mono ethanol amine 0.30 1050.00 Toluene 6.07 21245.00 Methyl aceto acetate 0.27 945.00 Liq ammonia 0.64 2240.00 Ethyl Chloroaceto acetate 0.37 1295.00 Hydrochloric Acidl 0.03 105.00 Acetic acid 0.29 1015.00 Sodium chloride 0.33 1155.00 Sodium hydride 0.19 665.00 Ortho Chlorobenzaldehyde 0.27 945.00 Hexane 1.28 4480.00 Piperidine 0.01 35.00 Ethyl acetate 2.34 8190.00 Hexane 2.38 8330.00 2,4-Dihydro-4-[4-[4-(4- 1-(4 -Methyxy) piperadine 0.94 3290.00 methoxyphenyl)-1- Paranitrochlorobenzene 0.77 2695.00 piperazinyl]phenyl]-2-(1- Potassium carbonate 1.38 4830.00 methylpropyl)-3H-1,2,4-triazol- Dimethyl formamide 11.70 40950.00 3-one Methanol 2.19 7665.00 Acetone 2.22 7770.00 Carbon 0.02 70.00 Palladium carbon 0. 01 35.00

Page 25 of 179

Hydrogen gas 0.11 385.00 Phenyl chloroformate 0.85 2975.00 Sodium bicarbonate 0.76 2660.00 Methylene chloride 2.65 9275.00 Hydragin hydrate 0.69 2415.00 n-Butanol 1.59 5565.00 Formamidine acetate 0.69 2415.00 2-Bromo butane 1.34 46 90.00 Hydrochloric acid 0.41 1435.00 Montelukast sodium Acetic acid 0.43 1075.00 Acetone 10.67 26675.00 Activated Carbon 0.10 250.00 Di isopropyl ethylamine 0.04 100.00 Hydrochloric acid 0.37 925.00 Methylene Dichloride 12.00 30000.00 (MDC) Methane sulfonyl chloride 0.10 250.00 Methanol 14.80 37000.00 N-vinyl pyrolidone 0.72 1800.00 Sodium chloride 0.80 2000.00 Sodium hydroxide 0.58 1450.00 Tertiary Butyl amine 0.20 500.00 Thiol Acetic acid 0.49 1225.00 Thiophene-2-ethylamine 2.32 5800.00 Toluene 48.00 120000.00 Valsartan L-Valine 0.45 1125.00 Thionyl Chloride 0.46 1150.00 Methanol 8.00 20000.00 Toluene 25.00 62500.00 4-Bromomethyl-biphenyl- 0.82 2050.00 2-carbonitrile Potassium carbonate 0.45 1125.00 Valeryl Chloride 0.34 850.00 Tri Ethyl Amine 0.20 500.00 Sodium Azide 0.16 400.00 Sodium Bicarbonate 0.25 625.00 Sodium Sulphate 0.10 250.00 Tri Butyl tin Chloride 0.80 2000.00 Hydrogen Gas 0.01 25.00 Sodium Hydroxide 0.20 500.00 Xylene 2.40 6000.00 Methylene Dichloride 5.00 12500.00 Acetic acid 0.40 1000.00 N-Hexane 2.00 5000.00 Activated Carbon 0.10 250.00 Venlafaxine Hydrochloride 4-Methoxy Benzoyl Cyanide 0.97 2425.00

Page 26 of 179

Methanol 3.50 8750.00 Sodium Methoxide 0.9 1 2275.00 Cyclohexanone 0.90 2250.00 Toluene 4.81 12025.00 Acetic Acid 8.15 20375.00 Tetra butyl ammonium 0.05 125.00 bromide Sodium hydroxide 4.77 11925.00 formic soda 1.94 4850.00 Formaldehyde 1.12 2800.00 Hydrochloric acid 2.51 6275 .00 Ethyl acetate 22.53 56325.00 Sodium Sulphate 0.27 675.00 Sodium chloride 0.34 850.00 Hyflowsupercell 0.04 100.00 IsoPropylAlcohol 14.6 36500.00 IsoPropyl Alcohol HCl 1.09 2725.00 Activated Charcoal 0.01 25.00 LevocetirizineDihydrochloride 1-[((4 0.92 22300.00 Chlorophenyl)phenyl)methyl] -4- [(phenylsulphonyl)]piperazine 2(2-Chloroethoxy )acetamide 0.29 725.00 4-Hydroxy benzoic acid 0.32 800.00 Hydrobromic acid 0.17 425.00 Sodium hydroxide 0.17 425.00 Hydrochloric acid 0.31 775 .00 Sodium carbonate 0.23 575.00 Potassium iodide 0.03 75.00 Toluene 30.30 75750.00 Methylene Dichloride 37.20 93000.00 Acetone 9.30 23250.00 Activated carbon 0.08 200.00 Pregabalin Sodium Hydroxide 1.90 4750.00 R-(-)-3- (Carbamoyl 1.37 3425.00 methyl)-5-methyl hexanoic acid Liquid Bromine 1.23 3075.00 Hyflosupercell 0.07 175.00 Activated carbon 0.02 50.00 Hydrochloric acid 2.46 6150.00 Iso Propyl Alcohol 7.06 17650.00 Veratric Acid Catechol 0.92 2300.00 Sodium Hydroxide 0.76 1900.00 Dimethyl Sulphate 2.30 5750.00 Aluminium Chloride 1.32 3300.00

Page 27 of 179

Acetyl Chloride 1.04 2600.00 Methylene Dichloride 5.74 14350.00 Hydrochloric Acid 3.00 7500.00 Sodium Hypo Chlorite 12.30 30750.00 Activated C arbon 0.02 50.00 Sodium meta bi sulphate 0.07 175.00 Sodium Bicarbonate 0.02 50.00 Fluconazole 1,2,4 -Triazole 0.66 2310.00 1,3-Diflurobenzene 0.80 2800.00 4-amino -1,2,4 -Triazole 0.65 2275.00 Aluminum Chloride 0.96 3360.00 Ammonia Solution 3.36 11760.00 Activated Carbon 0.06 210.00 Chloroacetyl Chloride 0.84 2940.00 Citric acid 0.06 210.00 Hydrochloric Acid 2.02 7070.00 Hyflowsupercell 0.05 175.00 IsoPropylAlcohol 3.16 11060.00 Methylene Chloride 4.80 16800.00 Potassium Hydroxide 0.94 3290.00 Sodium bicarbonate 0.06 210.00 Sodium Nitrite 0.47 1645.00 Toluene 8.40 29400.00 Trimethylsulphoxonium 1.32 4620.00 iodide Itraconazole 1-(4-MethyxyPhenyl) 1.02 3570.00 piperazine 1H,1,2,4 -Triazole 0.83 2905.00 2-Bromo butane 0.39 1365.00 Acetone 0.06 210.00 Activated Carbon 0.09 315.00 Cis-Bromobenzoate 1.31 4585.00 Dimethyl formamide 0.52 1820.00 Ethyl acetate 0.14 490.00 Formamidine acetate 0.75 2625.00 Hydragin hydrate 0.76 2660.00 Hydro bromic acid 0.31 1085.00 Hydrochloric acid 0.45 1575.00 Hydrogen gas 0.12 420.00 Hyflowsupercell 0.08 280.00 Methane sulfonyl chloride 0.45 1575.00 Methanol 0.30 1050.00 Methylene chloride 0.15 525.00 n-Butanol 0.03 105.00 Palladium c arbon 0.00 35.00 Paranitrochlorobenzene 0.84 2940.00

Page 28 of 179

Phenyl chloroformate 0.92 3220.00 Potassium carbonate 2.75 9625.00 Potassium hydroxide 0.61 2135.00 Sodium carbonate 1.02 3570.00 Sodium bicarbonate 0.84 2940.00 Sodium hydroxide 0.21 735.00 Toluene 0.11 385.00 Triethyl amine 0.47 1645.00 Cetirizine Dihydrochloride 4-Chloro 0.92 3220.00 benzhydrylpiperazine Toluene 8.20 28700.00 2-Chloroethanol 0.46 1610.00 Triethylamine 1.00 3500.00 Sodium carbonate 0.40 1400.00 Sodium monochloro acetate 0.70 2450.00 Potassium hydroxide 0.34 1190.00 Dimethylformamide 0.20 700.00 Methylene dichloride 3.00 10500.00 Acetone 3.00 10500.00 Hydrogen chloride 0.52 1820.00 Activated carbon 0.15 525.00 Rabeprazole sodium 2,3 Lutidin e 0.46 230.00 Acetic acid 0.46 230.00 Hydrogen peroxide 0.33 165.00 Nitric acid 0.30 150.00 Sulfuric acid 1.08 540.00 3-Methoxy-1 -propanol 0.40 200.00 Acetic anhydride Sodium hydroxide 0.67 335.00 Toluene 13.5 6750.00 Dimethyl Sulph oxide 2.00 1000.00 Acetic anhydride 1.50 750.00 Hydrochloric Acid 0.20 100.00 Thionyl chloride 0.53 265.00 Sodium sulphate 0.10 50.00 Methylene Dichloride 13.50 6750.00 2-mercapto benzimidazole 0.53 265.00 Sodium hypochlorite (8%) 3.27 1635.00 Acetone 1.50 750.00 Sodium Hydro Sulphate 0.12 60.00 Mono Methyl Amine in 0.10 50.00 Methanol Isopropyl Alcohol 3.00 1500.00 Activated Carbon 0.10 50.00 Pranklukast 4-(4-phenylbutoxy) benzoic 1.00 3500.00 acid

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1-(3-amino-2-hydroxyphenyl) 0.58 2030.00 ethanone Methylene Dichloride 5.88 20580.00 Dimethyl Formamide 0.05 175.00 Thionyl Chloride 0.59 2065.00 Pyridine 0.90 3150.00 Hydrochloric acid 3.00 10500.00 Sodium Bicarbonate 0.30 1050.00 Sulfuric Acid 5.00 17500.00 Ethyl Acetate 9.00 31500.00 Zonisamide Methanol 1.22 610.00 4HydroxyCoumarin 1.56 780.00 Hydroxylamine hydrochloride 2.34 1170.00 Potassium acetate 3.30 1650.00 Sodium Hydroxide 0.16 80.00 Methylene dichloride 3.92 1960.00 Hydrochloric Acid 0.80 400.00 Ethylene dichloride 6.85 3425.00 1,4 Dioxane 0.78 390.00 Chlorosulfonic acid 0.96 480.00 Sodium Sulphate 0.62 310.00 Toluene 2.40 1200.00 Phosphorus Oxychloride 0.16 80.00 Ammonia Gas 1.04 520.00 Ethyl Acelate 11.56 5780.00 Activated Carbon 0.06 30.00 Hyflowsupercell 0.06 30.00 Telmisartan Acetone 1.34 3350.00 Acetic acid 2.14 5350.00 Activated carbon 0.06 150.00 Bibenzimidazole 0.85 2125.00 Bromo methyl ester 0.85 2125.00 Celite 0.04 100.00 Dimethyl formamide 8.60 21500.00 Methanol 29.38 73450.00 Potassium hydroxide 0.35 875.00 Sodium hydroxide 0.15 375.00 Recoveries ( -) Acetone 1.27 3175.00 Rosuvastatine calcium 4-Fluoro benzaldehyde 0.52 260.00 4-Methyl-3-oxo-pentanoic 0.66 330.00 acid ethyl ester Potassium hydroxide 0.24 120.00 Methyl Iodide 0.60 300.00 Methanol 5.50 2750.00 S-Methyl isothio urea 0.35 175.00 2,3-Dichloro-5,6-dicyano 0.85 425.00

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benzoquinone Hexamethylphosphoramide 1.00 500.00 Methylene dichloride 8.00 4000.00 Meta chloroperoxy benzoic 1.19 595.00 acid Methyl amine 0.10 50.00 Ethanol 2.50 1250.00 Methane sulfonyl chloride 0.35 175.00 Sodium hydride (60%) 0.01 5.00 Di methoxy ethane 3.00 1500.00 Hydrogen gas 0.01 5.00 Diisobutylaluminium hydride 0.01 5.00 Toluene 8.00 4000.00 Methyl(3R)-3-(tert butyl di 1.45 725.00 methyl silyloxy)-5-oxo-6- tri phenyl phosphoranylidenehexanoate Triethyl amine 0.15 75.00 N,N -Dimethyl formamide 3.00 1500.00 Hydrogen fluoride 0.05 25.00 Tet ra Hydro Furan 2.50 1250.00 Ethyl acetate 10.50 5250.00 Diethyl methoxyborane 0.20 100.00 Sodium boro hydride 0.01 5.00 Calcium chloride 0.13 65.00 Posaconazole 4-Hydroxyphenyl- 1.40 2100.00 piperazinyltriazolone (5R,Cis)-toluene-4-sulfonic 1.40 2100.00 acid-5-(2,4-difluorophenyl)-5- (1H-1,2,4-triazol-1-yl)methyl tetrahydrofuran-3-yl methylester Sodium Hydroxide 0.90 1350.00 Hydrochloric Acid 0.80 1200.00 Sodium Chloride 1.40 2100.00 Ethyl Acetate 14.00 21000.00 Dimethyl Sulfoxide 11.00 16500.00 Isopropyl Alcohol 83.00 1124500.00 Hydrogen gas 0.05 75.00 Methanol 23.00 34500.00 Acetone 19.00 28500.00 Palladium Carbon 0.90 1350.00 Methylene Dichloride 9.00 13500.00 Ursodiol Chenodeoxycholic acid 2.75 4125.00 Acetone 90.70 136050.00 N-Bromosuccinamide 2.24 3360.00 Potassium tertbutoxide 2.44 3360.00 Page 31 of 179

Ranney Nickel 0.96 1440.00 Ethyl acetate 8.08 12120.00 Isopropyl alcohol 34.20 51300.00 Hydrochloric Acid 2.10 3150.00 Triethylamine 0.55 825.00

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ANNEXURE - III ______BRIEF MANUFACTURING PROCESS DESCRIPTION

Group – I

1. Phenylephrine HCl

Process Description: M-hydroxyacetophenone reacts with bromine in presence of aluminium chloride to form M- hydroxyl bromoacetophenone which will react with N-methyl benzyl amine in presence of Ranney Nickel to obtain phenylephrine hydrochloride.

Route of Synthesis:

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Material Balance:

Stage -I Input QTY.(kgs) Output QTY.(kgs) m-hydroxyacetophenone 350 Stage - I Mass 500 Ethyl acetate 700 HBr 210 An.Aluminium chloride 17.5 Solvent Liq. Bromine 204 Toluene recovery 665 Toluene 700 Toluene loss 21 n-methyl benzyl amine 258 Ethyl acetate recovery 665 Water 250 Ethyl acetate loss 21 Acidic isopropyl a lcohol 75 Liquid waste Water 250 Aluminum chloride 17.5 Toluene 14 Ethyl acetate 14 Acidic Isopropyl alcohol 75 Solid waste 0 Gaseous waste 0 Organic residue 102 Total 2554.5 Total 2554.5

Stage-II Input QTY.(kgs) Output QTY.(kg s) Stage - I Mass 500 Stage - II mass 400 Methanol 2500 Solvent Ranney nickel (10% charcoal) 25 Methyl recovery 2250 Hydrogen gas 2 Methyl loss 125 Hyflow powder 2 Liquid waste Water 250 Water 250 Methanol 63 Organic 92 Solid waste 99 Gas eous waste 0 Organic residue 0 Total 3279.0 Total 3279.0

Stage-III Input QTY.(kgs) Output QTY.(kgs) Stage - II Mass 400 Stage - III Mass 375 Isopropyl alcohol 2000 Solvent HCl 88 Isopropyl alcohol recovery 1800 water 250 Isopropyl alcohol loss 10 0 Acidic isopropyl alcohol 200 Liquid waste Water 250 Isopropyl alcohol 100 Acidic isopropyl alcohol 200 Solid waste 113 Gaseous waste 0

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Organic residue 0 Total 2938 .0 Total 293 8.0

Stage -IV Input QTY.(kgs) Output QTY.(kgs) Stage- III Mass 375 Phenylephrine HCL -Product 300 Isopropyl alcohol 2250 Solvent Activated charcoal 12 Isopropyl alcohol recovery 1800 Hyflow powder 2 Isopropyl alcohol loss 112.5 Liquid waste 0 Solid waste 351.5 Gaseous waste 0 Organic residue 75 Total 2639.0 Total 2639.0

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2. Ofloxacin

Process Description: Quonalinic acid & N- methyl piperizine reacted in butanol. The reaction mass acetic acid is added mass is neutralized to give ofloxacin. Purified, filtered & dried to give ofloxacin.

Route of Synthesis:

Material Balance:

Stage -I Input QTY.(kgs) Output QTY.(kgs) Quinolic Acid 125.00 Ofloxacin 100.00 N-methyl Piperazine 90.00 Butanol Rec 95.00 Butanol 100.00 Dry loss 20.00 Acetic Acid 30.00 Solvent Lo ss 05.00 Liq Ammonia 45.00 Aqu effluent 170.00 Total 390.00 Total 390.00

Page 36 of 179

3. Olanzapine

Process Description:

Charge Methyl piperazinylChloro-thieno benzodiazepine, N N DMA, catalyst heat and reflux distilled out. Add Acetonitrile cool & filters dry in RCVD to get Olanzapine.

Route of Synthesis:

Material Balance:

Stage-I Input QTY.(kgs) Output QTY.(kgs) Methyl piperazinyl 80.00 Olanzapine 75.00 Chloro -thieno benzodiazepine 100.00 Aqu. Effluent 280.00 N N DMA 400.00 Process loss 25.00 Cataly st 10.00 Solvent Recovery 510.00 Acetonitrile 300.00 Total 890.00 Total 890.00

Page 37 of 179

4. Hydrochlorothiazide

Process description: 5-Chloro Aniline 2-4 Disulphonamide in water reacted with Formaldehyde at 80°C gives Hydrochlorothiazide. Centrifuge the reaction mass, Give charcoal treatment and filter, dry the material.

Route of Synthesis:

Material balance:

Stage-I INPUT QTY.(KGS) OUTPUT QTY.(KGS) 5-Chloro Aniline 2-4 Disulphonamide 240 Hydrochlorothiazide 200 Sulphuric acid 32.2 Activated carbon 3.5 Methanol 79.2 Effluent 570.5 Formaldehyde 20.4 Sodium hydroxide 10 Hydrochloric acid 28.7 Activated carbon 3.5 Purified water 360 Total 774 Total 774

Page 38 of 179

5. Oxcabazepine

Process Description:

5H-Dibenz[b,f]azepine-5- carbonitrile ; Sodium nitrite treated in presence of Acetic acid & Iron Boron Trifluoride is added. The mass is filtered to give crude product, crystallized from IPA, filtered & dried to give Oxcabazepine.

Route of Synthesis:

Page 39 of 179

Material balance:

Stage -I Input QTY.(kgs) Output QTY.(kgs) 5H -Dibenz [b,f]azepine -5- carbonitrile 135.00 Stage -1 109.00 Sodium nitrite 68.00 Aqu. Effluent for Sodium nitrite 279.00 Acetic acid 185.00 Total 388.00 Total 388.00

Stage-II Input QTY.(kgs) Output QTY.(kgs) Stage -1 109.00 Stage -1 87.00 Iron 8.00 Aqu. Effluent for Fe Acetate 175.00 Acetic acid 110.00 Boron TriFluoride 35.00 Total 262.00 Total 262.00

Stage-III Input QTY.(kgs) Output QTY.(kgs) Stage -2 87.00 Oxcabazepine 100.00 IPA 225.00 IPA Rec 202.00 Dry Loss 10.00 Total 312.00 Total 312.00

Page 40 of 179

6. 10-Methoxy-5H-dibenz[b,f]azepine-5-carbonylchloride, 10- Methoxyiminostilbene-5-carbonylchloride

Process Description: 5H-Dibenz[b,f]azepine-5- carbonitrile ; Sodium nitrite treated in presence of Acetic acid & Iron Boron Trifluoride is added. The mass is filtered to give crude product, crystallized from IPA, filtered & dried to give Oxcabazepine.

Flow Chart:

5H-Dibenz [b,f]azepine-5-

carbonitrile

Sodium nitrite

Acetic acid

Iron

Acetic acid

Boron Trifluoride

Stage -1

10-Methoxy-5H-dibenz [b,f]azepine-5- carbonylchloride, 10-Methoxyiminostilbene-5- carbonylchloride

Material balance:

Stage -I Input QTY.(kgs) Output QTY.(kgs) 5H -Di benz [b,f]azepine -5- carbonitrile 135.00 Stage -1 109.00 Sodium nitrite 68.00 Aqu. Effluent for Sodium nitrite 279.00 Acetic acid 185.00 Total 388.00 Total 388.00

Page 41 of 179

7. Diclofenac Sodium

Process Description: Stage-I: 2,6 DCP, sodium methoxide, ethyl chloro acetate, aniline caustic are added to reactor inrequiredproportion.The mass is allowed to react together at required temperature and pressure condition, once the reaction is over, the material is filtered and dried in drier and packed in drums and stored as DCDPA Stage-II: DCDPA, ethoxy ethanol, chloro acetyl chloride are added to a reaction vessel, hydrogenchloride gas generated during the reaction is scrubbed off with the help of caustic solution in scrubber tower. The material filtered, washed and dried packed and store as CPDCA Stage-III: CPDCA, aluminium chloride to allow react in a reactor and controlled temperature condition.The mass is then quenched in water and filtered, hydrogen chloride gas generated during reaction and quenching is taken to scrubber system. Neutralized material is filtered, washed, dried, packed and store as Indolinone Stage-IV: Indolinone, caustic and solvent added reaction vessel, reaction is done under controlledcondition the material after reaction is over, filtered, and dried packed and stored as DFS.

Page 42 of 179

Material balance:

Stage -I Input QTY.(kgs) Output QTY.(kgs) 2,6 D.C.P 61.76 D.C.D.P.A 80.00 Sodium Methoxide soln.25% 145.60 Solvent Reco 184.00 Ethyl Chloro Acetate 43.52 NaCl 19.20 Aniline 33.92 Effluent 113 .60 Caustic Lye 22.00 Process loss 32.80 Water 12 2.80 Total 429 .60 Total 42 9.60

Stage-II Input QTY.(kgs) Output QTY.(kgs) D.C.D.P.A 80.00 C.P.D.C.A 100.00 Chloro Acetyl Chloride 58.00 HCL gas 15.00 Ethoxy ethanol 220.00 Solvent Reco 235.00 Dry Loss 8.00 Total 358.00 Total 358.00

Stage-III Input QTY.(kgs) Output QTY.(kgs) C.P.D.C.A 112.00 Indolinone 100.00 Aluminium Chloride 65.60 Aqu Effluent 110 .00 Water 83 .00 HCL 15.00 Drying Loss 35.60

Total 260 .60 Total 260 .60

Stage-IV Input QTY.(kgs) Output QTY.(kgs) Idolinone 109.00 Diclofenac Sodium 100.00 Sodium Hydroxide 30.20 Effluent 69.00 Water 60.00 Charcoal 1.00 Charcoal 0.8 Dry Loss 30.00 Total 200.00 Total 200.00

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8. 2,6 – dichloro diphenyl amine (dcdpa)

Process Description: 2,6 DCP, sodium methoxide, ethyl chloro acetate, aniline caustic are added to reactor inrequiredproportion.The mass is allowed to react together at required temperature and pressure condition, once the reaction is over, the material is filtered and dried in drier and packed in drums and stored as DCDPA.

Route of Synthesis:

Material balance:

Stage-I Input QTY.(kgs) Output QTY.(kgs) 2,6 D.C.P 61.76 D.C.D.P.A 80.00 Sodium Methoxide soln.25% 145.60 Solvent Reco 184.00 Ethyl Chloro Acetate 43.52 NaCl 19.20 Aniline 33.92 Effluent 183.60 Caustic Lye 22.00 Process loss 32.80 Water 192.80 Total 499.60 Total 499.60

Page 44 of 179

9. N-chloroacetyl-n-phenyl-2,6-dichloro aniline (cpdca)

Process Description:

Stage-I: 2,6 DCP, sodium methoxide, ethyl chloro acetate, aniline caustic are added to reactor inrequiredproportion.The mass is allowed to react together at required temperature and pressure condition, once the reaction is over, the material is filtered and dried in drier and packed in drums and stored as DCDPA.

Stage-II: DCDPA, ethoxy ethanol, chloro acetyl chloride are added to a reaction vessel, hydrogenchloride gas generated during the reaction is scrubbed off with the help of caustic solution in scrubber tower. The material filtered, washed and dried packed and store as CPDCA.

Route of synthesis:

Page 45 of 179

Material balance:

Stage-I Input QTY.(kgs) Output QTY.(kgs) 2,6 D.C.P 61.76 D.C.D.P.A 80.00 Sodium Methoxide soln.25% 145.60 Solvent Reco 184.00 Ethyl Chlor o Acetate 43.52 NaCl 19.20 Aniline 33.92 Effluent 183.60 Caustic Lye 22.00 Process loss 32.80 Water 192.80 Total 499.60 Total 499.60

Stage-II Input QTY.(kgs) Output QTY.(kgs) D.C.D.P.A 80.00 C.P.D.C.A 100.00 Chloro Acetyl Chloride 58.00 HCL gas 15.00 Ethoxy ethanol 220.00 Solvent Reco 235.00 Dry Loss 8.00 Total 358.00 Total 358.00

Page 46 of 179

10. Indolenone

Process Description: Stage-I: 2,6 DCP, sodium methoxide, ethyl chloro acetate, aniline caustic are added to reactor inrequiredproportion.The mass is allowed to react together at required temperature and pressure condition, once the reaction is over, the material is filtered and dried in drier and packed in drums and stored as DCDPA. Stage-II: DCDPA, ethoxy ethanol, chloro acetyl chloride are added to a reaction vessel, hydrogenchloride gas generated during the reaction is scrubbed off with the help of caustic solution in scrubber tower. The material filtered, washed and dried packed and store as CPDCA. Stage-III: CPDCA, aluminium chloride to allow react in a reactor and controlled temperature condition.The mass is then quenched in water and filtered, hydrogen chloride gas generated during reaction and quenching is taken to scrubber system. Neutralized material is filtered, washed, dried, packed and store as IndolinoneDiclofenac Sodium (DFS).

Route of Synthesis:

Page 47 of 179

Material Balance:

Stage-I Input QTY.(kgs) Output QTY.(kgs) 2,6 D.C.P 61.76 D.C.D.P.A 80.00 Sodium Methoxide soln.25% 145.60 Solvent Reco 184.00 Ethyl Chloro Acetate 43.52 NaCl 19.2 0 Aniline 33.92 Effluent 183.60 Caustic Lye 22.00 Process loss 32.80 Water 192.80 Total 499.60 Total 499.60

Stage-II Input QTY.(kgs) Output QTY.(kgs) D.C.D.P.A 80.00 C.P.D.C.A 100.00 Chloro Acetyl Chloride 58.00 HCL gas 15.00 Ethoxy ethanol 220 .00 Solvent Reco 235.00 Dry Loss 8.00 Total 358.00 Total 358.00

Stage -III Input QTY.(kgs) Output QTY.(kgs) C.P.D.C.A 112.00 Indolinone 100.00 Aluminium Chloride 65.60 Aqu Effluent 150 .00 Water 123 .00 HCL 15.00 Drying Loss 35.60

Total 300 .60 Total 300 .60

Page 48 of 179

11. 2-Hydroxymethyl-3-methyl-4-(3-methoxy propanoxyl) pyridine HCL

Route of Synthesis:

Page 49 of 179

Mass Balance:

STAGE-1 INPUT QTY.(KGS) OUTPUT QTY.(KGS) 2,3 Lutidine 46.00 Stage -1 65.00 Acetic acid 46.00 Spent acid 140.00 Hydrogen peroxide 33.00 Effluent 200.80 Nitric acid 30.00 Organic Residue 7.20 Sulfuric acid 108.00 Water 150.00 Total 413.00 Total 413.00

STAGE -2 INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage -1 65.00 Stage -2 80.00 3-Methoxy-1 –propanol 40.00 Toluene Reco 235.00 Acetic anhydride Sodium hydroxide 18.50 DMSO Reco 188.00 Toluene 250.00 Solvent loss 22.00 DMSO 200.00 Inorganic solid waste 29.70 Organic waste 11.80 Water generate 7.00 Total 573.50 Total 573.50

STAGE -3 INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage -2 80.00 Stage -3 90.00 Acetic anhydride 150.00 Toluene Reco 660.00 NaOH 20.00 Acetic anhydride Reco 107.00 HCL 20.00 Effluent 160.50 Toluene 700.00 Organic Residue 13.50 Water 100.00 Process loss 39.00 Total 107 0.00 Total 107 0.00

Page 50 of 179

12. 1,2-benisoxazole-3-acetica acid

Process Description: Stage-I: 4-Hydroxycoumarin was reacted with hydroxylamine HCl in presence of potassium acetate anhydrous in methanol at desired temperature and appropriate condition.

Route of Synthesis:

Mass Balance:

STAGE-I INPUT QTY.(KGS) OUTPUT QTY.(KGS) Methanol 153.00 Stage -1 214.00 4Hydroxy Coumarin 195.30 Methanol Reco 137.7 Hydroxylamine hydrochloride 293.00 Methanol loss 15.3 Potassium acetate 413.00 Effluent 838.30 Sodium hydroxide 20.00 Dry loss 30.00 Methylene Dichloride 290.00 Organic Residue 29.00 Hydroc hloric Acid 100.00 Water 300.00 Total 1264.30 Total 1264.30

Page 51 of 179

13. Cis-tosylate

Process Description:

Stage I: CBB is reacted with IMD in the presence of DMF as solvent. The reaction mass is quenched in sodium bicarbonate solution and the product is extracted with toluene. The aqueous layer is kept for IMD recovery. The organic layer containing the product is reacted with sodium hydroxide solution. After completion of reaction, the pH of the mass is adjusted with hydrochloric acid. mass is diluted with water and centrifuged. The wet cake is dissolved in ethyl acetate and treated with carbon. The mass is filtered and the ethyl acetate is distilled off. The residue is cooled and centrifuged. The mass is dried to produce KT-I.

Stage II: KT-I is reacted with PTSC in the presence of sodium carbonate and methylene chloride as solvent. The reaction mass is diluted and the organic layer separated. Methylene chloride is distilled off completely from the organic layer and the residue is diluted with methanol and water. The mass is centrifuges and washed with methanol and water mixture. The mass is dried to produce Cis-Tosylate (KT-II).

Route of Synthesis:

Page 52 of 179

Material Balance:

Stage -I Input QTY.(kgs) Output QTY.(kgs) CBB 780 Stage -1 450 IMD 693.3 IMD Rec 360 DMF 37.2 Toluene Rec 2207.0 Toluene 2275.5 Ethyle Acetate 1620.0 Sodium Bicarbonate 148.2 Aq. Effluent 15 99.4 Sodium hydroxide 120.0 Spent carbon 12.0 Water 705.0 Residue 130.0 HCl 156 Process loss 254.9 Ethyl Acetate 1706.4 Activated Carbon 6.0 Vacuum Salt 6.0 Total 66 33.3 Total 66 33.3

Stage -II Input QTY.(kgs) Output QTY.(kgs) Stage -1 450.0 Stage -2 600.0 Methylenechloride 3217.5 Methylenechloride Rec 3024.0 P-Toluene Sulfonyl Chloride 465.0 Methanol Rec 1375.0 Sodium Carbonate 307.5 Aq. Effluent 778.0 HCl 12.0 Process Loss 400 Methanol 1425.0 Water 420 Total 6297.0 Total 6297.0

Page 53 of 179

14. Atorvastatin Calcium

Process Description:

2R-trans)-5-(4-Fluorophenyl)-2-(1-Methyl)-N,4diphenyl-1-[2-Tetra hydroxy- 4hydroxy-6-Oxo- 2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide treated with NaOH in IPA. The mass is treated with calcium acetate solution. The crude obtained is crystallized from IPA to give atorvastatin calcium.

Route of Synthesis:

Page 54 of 179

Material Balance:

Stage -I Input QTY.( kgs) Output QTY.(kgs) (2R -trans) -5-(4 - Fluorophenyl) -2-(1 - Stage - 1 89.00 Methyl)-N,4diphenyl-1-[2- Tetra Aqu. Effluent for IPA Rec 358.00 hydroxy-4-hydroxy- 6-Oxo-2H-pyran-2- yl)ethyl]- 1H-pyrrole-3-carboxamide 191.00 IPA 225.00 NaOH 31 .00 Total 447.00 Total 447.00

Stage-II Input QTY.(kgs) Output QTY.(kgs) Stage – 1 89.00 Stage -2 101.00 Calcium Acetate solution 140.00 Aqu. Effluent for Calcium 128.00 Acetate solution Rec Total 229.00 Total 229.00

Stage-III Input QTY.(kgs) Output QTY.(kgs) Stage – 2 101.00 Atorvastatin Calcium 100.00 IPA 173.00 Aqu. Effluent for IPA Rec 155.00 Dry Loss 19.00 Total 274.00 Total 274.00

Page 55 of 179

15. Tert-Butyl (4R,6R)-2-[[[6-(2-4-fluorophenyl)-5-isopropyl-3-phenyl-4- (phenylcarbamoyl)pyrrol-1-yl]ethyl]-2,2-dimethyl-1,3-dioxan-4-yl]acetate

Process Description:

2R-trans)-5-(4-Fluorophenyl)-2-(1-Methyl)-N,4diphenyl-1-[2-Tetra hydroxy- 4hydroxy-6-Oxo- 2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide treated with NaOH in IPA.

Route of Synthesis:

Material Balance:

Stage-I Input QTY.(kgs) Output QTY.(kgs) (2R -trans) -5-(4 - Fluorophenyl) -2-(1 - Stage - 1 89.00 Methyl)-N,4diphenyl-1-[2- Tetra Aqu. Effluent for IPA Rec 358.00 hydroxy-4-hydroxy- 6-Oxo-2H-pyran-2- yl)ethyl]- 1H-pyrrole-3-carboxamide 191.00 IPA 225.00 NaOH 31.00 Total 447.00 Total 447.00

Page 56 of 179

16. Nebivolol hydrochloride

Process Description:

Benzopyran-2-Carboxaldehyde Derivative treated with Trimethylsulfoxonium iodide In presence of Potassium hydroxide & Water. The mass is further treated with Benzyl amine & Toluene, Ammonium formate using Pd/Catalyst. The mass is crystallized from Methanol, filtered & dried to give Nebivolol.

Route of Synthesis:

Page 57 of 179

Material Balance:

Stage-I Input QTY.(kgs) Output QTY.(kgs) Benzopyran -2- CarboxaldehydeDerivative 140.00 Stage -1 81.00 Trimethylsulfoxonium iodide 115.00 Aqu. Effluent 430.00 Potassium hydroxide 56.00 Water 200.00 Total 511.00 Total 511.00

Stage -II Input QTY.(kgs) Output QTY.(kgs) Stage -1 81.00 Stage -2 121.00 Benzyl amine 40.00 Toluene Rec 270.00 Toluene 300.00 Solvent Loss 30.00 Total 421.00 Total 421.00

Stage -III Input QTY.(kgs) Output QTY.(kgs) Stage -2 121.00 Stage -3 168.00 Ammonium formate 60.00 Methanol Rec 108.00 Hydrogen gas 1.00 Solve nt Loss 12.00 Methanol 120.00 Hydrogen gas 1.00 Process loss 13.00 Total 302.00 Total 302.00

Stage-IV Input QTY.(kgs) Output QTY.(kgs) Stage -3 168.00 Nevivolol 100.00 Methanol 400.00 Methanol Rec 360.00 Solvent Loss 40.00 Dry loss 28.00 Carbon dioxide 40.00 Total 568.00 Total 568.00

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17. Pantaprazol Sodium

Process Description:

Pantoprazole chloro compound will react with 5-difluoromethoxy-2-mercapto benzamidazole in presence of Base in organic solvent to get PT-S compound. PT-S compound will react with sodium hypochlorite in presence of organic solvent to get PT-1 compound. PT-1 compound will reacts with sodium hydroxide in presence of organic solvent to get Pantoprazole sodium sesquihydrate.

Route of Synthesis:

Page 59 of 179

Material Balance:

Stage-1 Input QTY.(KGS) Output QTY.(kgs) Pantoprazole chloro compound 77 Stage-1 115 Diflouro Methoxy-2-MB 73.5 IPA MLs 627 NaOH 30 Evaporation loss 15.1 R.O. water 200.50 Evaporation loss 8.4 IPA 462 Aq. layer 77.5 Total 843 Total 843

Stage-2 Input QTY.(KGS) Output QTY.(kgs) Stage-1 115 Stage-2 103.5 10% NaOCl 279 Evaporation loss 8 IPA 692 IPA MLs 885 R.O. water 186.5 Evaporation loss 4 Aq. layer 272 Total 1272.5 Total 1272.5

Stage-3 Input QTY.(KGS) Output QTY.(kgs) Stage-2 103.5 Pantoprazole Sodium- API 100 NaOH 11 Evaporation loss 10 Acetone 623 Evaporation loss 7 R.O. water 18 Acetone MLs 638.5 Total 755.5 Total 755.5

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18. 5-(Difluoromethoxy)-2- {[( 3,4Dimethoxypyridin - 2-yl) methyl]thio}-1H- benzimidazole

Process Description:

Pantoprazole chloro compound will react with 5-difluoromethoxy-2-mercapto benzamidazole in presence of Base in organic solvent to get PT-S compound. PT-S.

Route of Synthesis:

Material Balance:

Stage-1 Input QTY.(KGS) Output QTY.(kgs) Pantoprazole chloro compound 77 Stage-1 115 Diflouro Methoxy-2-MB 73.5 IPA MLs 627 NaOH 30 Evaporation loss 15.1 R.O. water 291.50 Evaporation loss 8.4 IPA 462 Aq. layer 168.5 Total 934 Total 934

Page 61 of 179

19. N-((4-Chloromethyl)-2-Thiozolyl) Guanidine Hydrochloride

Process Description:

Stage-1: 1, 3-Dichloro acetone reacts with Guanylthiourea in the presence of Acetone as solvent media to give Stage-2 as product.

Route of Synthesis:

Material Balance:

Stage-1 Input Qty. Output Qty 1,3-Dichloro acetone 53.00 Stage-1 88.97 Guanylthiourea 50.00 Acetone Rec. 161.00 Potassium Iodide 2.40 Generated water 7.51 Acetone 170.00 Inorganic solid waste 2.40 Organic solid waste 7.52 Solvent Loss 8.0 Total 275.40 Total 275.40

Page 62 of 179

20. Methyl 3-amino-2 butenoate

Process Description: STAGE –1A: Charge Methyl acetoacetate and ammonia solution into the reactor and maintain for 6 hours. Filter the mass.

Route of Synthesis:

Material Balance:

Stage -1A INPUT QTY.(KGS) OUTPUT QTY.(KGS) Methyl aceto ac etate 40 Stage 1A 35 Liq ammonia 96 Aq. Effluent 111 Total 146 Total 146

Page 63 of 179

21. 2,4-Difluoro-2-(1h- 1,2,4-Triazole-1-Yl) Acetophenone (Dfta)

Process Description:

Stage-I: Charge Methylene dichloride and aluminium chloride into the reactor. Cool the mass to below 5°C. Charge 1,3-Difluorobenzene into the reactor. Add slowly chloroacetyl chloride into the reactor for 4 to 5 hours below 10°C. Charge the reaction mass to ice and hydrochloric acid. Stir the reaction mass for 4 hours and separate the layers. Distil off MDC completely below 50°C. Charge isopropyl alcohol and 4-amino-1,2,4-triazole into the reactor and maintain for 6 hours at 45-50°C. Cool the reaction mass to 10°C and centrifuge material and dry to produce 2-(1H-1,2,4-triazole-1-yl)-2’,4’-difluoroacetophenone salt.

Route of Synthesis:

Material Balance:

Stage -I Input QTY.(KGS) Output QTY.(KGS) 1,3 -Difluorobenzene 200 Stage -I Compound 480 Aluminium Chloride 240 Sol Rec(MDC) 1050 Methylene Chloride 1200 Sol Rec (IPA) 740 Chloroacetyl chlo ride 210 AlCl3 gel for Rec. 1100 4-Amino -1,2,4 -Triazole 162 Aq. Effluent 490 IPA 790 Residue 30 Sodium bicarbonate 15 Solvent loss 202 Hydrochloric acid 75 Ice & Water 1200 Total 4092 Total 4092

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22. cis-2-(2,4-Dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4- ylmethyl methane sulphonate

Route of Synthesis:

Page 65 of 179

Mass Balance:

Stage-01 Int-A INPU T QTY.(KGS) OUTPUT QTY.(KGS) Cis -Bromobenzoate 111.3 Triazole derivative 95.8 1H,1,2,4 -Triazole 70.4 Solvent rec (DMF) 181.7 Potassium carbonate 105.7 Solvent rec (Tol) 153.3 Dimethyl formamide 186.7 Aq. Effluent 238 .3 Sodium hydroxide 10.6 Residue 64 .5 Toluene 157.4 Solvent loss 9.1 Water 100 .7 Total 742 .7 Total 742 .7

Stage-02 Int-A INPUT QTY.(KGS) OUTPUT QTY.(KGS) Triazole derivative 95.8 ITR -INT -A 101.5 Triethyl amine 40.2 Solvent rec (MDC) 187.0 Methane sulfonyl chloride 38.3 Aq. Efflu ent 92.0 Methylene chloride 193.8 Spent carbon 7.7 Activated Carbon 3.8 Residue 56.2 Sodium hydroxide 6.9 Solvent loss 6.8 Water 72.4 Total 451.2 Total 451.2

Page 66 of 179

23. 1-(4-Methoxyphenyl)-1-(4-nitrophenyl) piperazine

Route of Synthesis:

Mass Balance:

Stage -01 INPUT QTY.(KGS) OUTPUT QTY.(KGS) 1-(4 -Methyxy) piperadine 86.9 Stage -I 132.4 Paranitrochlorobenzene 71.2 Solvent Rec (Methanol) 198.9 Potassium carbonate 77.1 Solvent Rec (Acetone) 200.2 Dimethyl formamide 101.5 Solvent Rec (DMF) 98.1 Methanol 203.3 Aq. Effluent 176.5 Acetone 205.7 Spent carbon 3.5 Carbon 1.7 Residue 54.8 Water 130.3 Solvent loss 13.3 Total 877.7 Total 877.7

Page 67 of 179

24. 2-[[4-(2-Methoxyethyl)phenoxy]methyl-oxirane

Process Description: Water take in Reactor add Epichlorohydrine and charge in 4.Methoxy Ethyl Phynol. After completing reaction we will get the product.

Route of Synthesis:

Mass Balance:

STAGE -1 (Epoxide) INPUT QTY.(KGS) OUTPUT QTY.(KGS) 4MEP 100.00 Epoxide 126.00 Epichlorohydrine 100.00 Effluent 35 4.00 Caustic soda 30.00 Water 250 .00 Total 48 0.00 Total 48 0.00

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25. 3''-acetyl-2''-hydroxy-4-(4 phenylbutoxy) benzanilide

Route of Synthesis:

Mass Balance:

Stage-1 Input QTY. (kgs) Output QTY. (kgs) 4-(4 -phenylbutoxy)benzoic acid 100.00 Stage -1 125.00 1-(3-amino-2-hydroxyphenyl) 57.60 Methylene Dichloride(Reco) 570.00 Ethanone Methylene Dichloride(F/R) 588.00 Solvent Loss 18.00 Dimethyl Formamide 5.00 Effluent 519.30 Thionyl Chloride 59.00 Organic Residue 27.10 Pyridine 89.60 Process Emissions(SO2) 19.80 Hydrochloric acid 200.00 Sodium Bicarbonate 30.00 Water 15 0.00 Total 1279.20 Total 1279.20

Page 69 of 179

Group – II

26. Prasugrel Hydrochloride

Process Description: Stage-I: Charge 2-Bromo-1-cyclopropyl-2-(2-flourophenyl)ethanone, 5,6,7,7a-tetrahydrothieno[3,2- c]pyridine-2-(4H)-one, potassium hydroxide and MeOH. Heat the reaction mass to reflux for 4 hrs. Cool the reaction mass to RT. Filter the reaction mixture distil off solvent from the filtrate and water to residue and cool it to 0-5°C. Filter the solid formed spin dry and unload the material dry the material at 50-60°C for 2 hrs. Cool the drier and unload the material. Stage-II: Charge stage-I material,Methyl Ethyl Ketone, and acetic anhydride, heat the reaction mass to reflux for 4 hrs. Cool the reaction mass to 5-10°C and filter spin, dry and unload the material. Dry the material at 50-60°C for 2hrs. Cool the drier and unload the material (Prasugrel). Stage-III: Charge Stage-II material, methanol andHCl and heat the reaction mass to reflux for 4 hrs. Cool the reaction mass and filter, spin, dry and unload the material. Dry the material at 50- 60°C for 2 hrs. Cool the drier and unload the material (prasugrel crude). Stage-IV: Charge Stage-III material, Acetone and Methanol. Heat the reaction mass to reflux for 2 hrs. Cool the reaction mass to 0-5°Cand filter, spin, dry and unload the material. Dry the material at 50-60°C for 2 hrs cool the drier and unload the material.

Page 70 of 179

Route of Synthesis:

Page 71 of 179

Material Balance:

Stage -I INPUT QTY.(KGS) OUTPUT QTY.(KGS) 2-Bromo-1-cyclopropyl-2-(2- 44 Stage-I 49 flourophenyl)ethanone Recovery Methanol 123 5,6,7,7a-tetrahydrothieno[3,2- 27 Loss of Methanol 9 c]pyridine-2-(4H)-one Effluent 364.86 Potassium Hydroxide 11 Residue 8.14 Methanol 132 Purified water 340 Total 554 Total 554

Stage-II INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage-I 49 Stage-II 50 Acetic anhydride 16 Recovery Methyl ethyl ketone 137 Methyl ethyl ketone 147 Loss of Methyl ethyl ketone 10 Residue 15 Total 212 Total 212

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Stage -III INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage-II 50 Stage-III 52 Hydrogen Chloride 5 Recovery Methanol 142 Methanol 150 Loss of Methanol 8 Residue 3 Total 205 Total 205

Stage-IV INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage-III 52 Prasugrel Hydrochloride 50 Acetone 156 Recovery Acetone 147.5 Methanol 156 Recovery Methanol 148 Loss of Acetone 8.5 Loss of Methanol 8 Residue 2 Total 364 Total 364

Page 73 of 179

27. 5-[2-Cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl] -5,6,7,7a- tetrahydrothieno[3,2-c]pyridin-2(4H)-one

Process Description:

Stage-I: Charge 2-Bromo-1-cyclopropyl-2-(2-flourophenyl)ethanone, 5,6,7,7a-tetrahydrothieno[3,2- c]pyridine-2-(4H)-one, potassium hydroxide and MeOH. Heat the reaction mass to reflux for 4 hrs. Cool the reaction mass to RT. Filter the reaction mixture distil off solvent from the filtrate and water to residue and cool it to 0-5°C. Filter the solid formed spin dry and unload the material dry the material at 50-60°C for 2 hrs. Cool the drier and unload the material.

Route of Synthesis:

Material Balance:

Stage-I INPUT QTY.( KGS) OUTPUT QTY.(KGS) 2-Bromo-1-cyclopropyl-2-(2- 44 Stage-I 49 flourophenyl)ethanone Recovery Methanol 123 5,6,7,7a-tetrahydrothieno[3,2- 27 Loss of Methanol 9 c]pyridine-2-(4H)-one Effluent 364.86 Potassium Hydroxide 11 Residue 8.14 Methanol 132 Purified water 340 Total 554 Total 554

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28. Dabigatran

Process Description: Stage-I: The propanoic acid methyl ester derivate of formulae-I is dissolved in ethanol and acetic acid hydrogenated with damp Pd/C at RT at 2 bar hydrogen pressure. After completion of the reaction the catalyst is filtered off and dissolved in ethanol was added to filtrate. To get formulae-II precipitated out which was filtered off and dried.

Stage-II: The Tosylate salt obtained in the stage-I was dissolved in acetone and the mixture is combined with hexyl chloroformate in presence of potassium hydroxide at temperature 15°C. After completion of the reaction the precipitated product is filtered off and washed with acetone mixture. The resulting crude is crystallized with water.

Route of Synthesis:

Material Balance

Stage -I INPUT QTY.(KGS) OUTPUT QTY.(KGS) 3-[(1-Methyl-2-{[4-(5-oxo-4,5-dihydro- 48.5 Stage-I 42.3 [1,2,4]oxadiazol-3-yl)-phenylamino]- Recovery Ethanol 1225 methyl)-1H benzoimidazole- Loss of Methanol 25 5carbonyl)-pyridin-2-ylamino]- Carbon dioxide 3.7 propionic acid ethyl ester Residue 25 P-toluene sulphonic acid 12.5 Acetic acid 10 Ethanol 1250 Total 1321 Total 1321

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Stage -II INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage-I 42.3 Dabigetran 50 Hexachlorofomate 14 Recovery Acetone 574.8 Acetone 600 Loss of Acetone 25.2 Potassium Hydroxide 4.8 Potassium chloride 6.3 Hydrochloric acid 0.19 Effluent 501.6 Purified water 500 Residue 3.3 Total 1161.2 Total 1161.2

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29. Famotidine

Process Description: Stage-1: 1, 3-Dichloro acetone reacts with Guanylthiourea in the presence of Acetone as solvent media to give Stage-2 as product. Stage-2: Stage-1 product reacts with Thiourea, N-Sulfamyl-3-chloropropionamidine, Sodium hydroxide and acetic acid in the presence of Methanol as solvent media to give Stage-2 as product. Stage-3 Stage-2 product reacts with ammonia in the presence of Methanol as solvent media to give Famotidine as product.

Chemical Reaction:

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Material Balance:

Stage -1 Input Qty. Output Qty 1,3 -Dichloro acetone 53.00 Stage -1 88.97 Guanylthiourea 50.00 Acetone Rec. 161.00 Potassium Iodide 2.40 Generated water 7.51 Acetone 170.00 Inorganic solid waste 2.40 Organic solid waste 7.52 Solvent Loss 8.0 Total 275.40 Total 275.40

Stage -2 Input Qty. Output Qty Stage-1 88.97 Stage-2 125.70 Thiourea 25.13 Methanol Rec. 3228.00 Sodium Hydroxide 40 Generated water 12.00 N-Sulfamyl-3- 74.00 Inorganic solid waste 70.60 chloropropionamidineHCl Acetic acid 20.00 Organic solid waste 39.80 Methanol 3397.00 Solvent loss 169.00 Total 3645.10 Total 3645.10

Stage -3 Input Qty. Output Qty Stage-2 125.70 Famotidine 100.00 Ammonia (23%) 24.00 Methanol Rec. 36.00 Acetic acid 5.00 Effluent Water 574.00 Activated Carbon 6.00 Spent Carbon 6.00 Water 525.00 Organic Residue 7.70 Solvent loss 1.00 Total 724.70 Total 724.70

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30. N-[(2'-Cyano[1,1'-biphenyl]-4-yl)methyl]-L valine methyl ester

Route of Synthesis:

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Mass Balance:

Stage-I Input QTY.(kgs) Output QTY.(kgs) L-Valine 45.00 Stage -1 50.00 Thionyl Chloride 45.70 Methanol Rec. 758.00 Methanol 800.00 Toluene Rec. 474.00 Toluene 500.00 Organic Residue 8.33 Solvent Loss 65.00 Process Loss 35.37 Total 1390.70 Total 1390.70

Stage-II Input QTY.(kgs) Output QTY.(kgs) Stage -1 50.00 Stage -2 90.00 4-Bromomethyl -biphenyl -2- carbonitrile 82.00 Toluene Rec. 565.00 Potassium carbonate 45.00 Effluent Water 569.78 Toluene 600.00 Organic Residue 9.22 Water 500.00 Process Loss 13.00 Solvent Loss 30.00 Total 1277.00 Total 1277.00

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31. Amlodipinbesylate

Process Description: Stage I: Charge toluene, phthalic anhydride and mono-ethanol amine into the reactor. Heat the mass to reflux. Maintain for 4 hours at reflux. After completion of the reaction, cool the mass below 35°C and charge water. Stir the mass and settle for 1 hour. Discard bottom aqueous layer to ETP. Cool the mass to 10-15°C. Centrifuge the material and wash with toluene. STAGE –1A: Charge Methyl acetoacetate and ammonia solution into the reactor and maintain for 6 hours. Filter the mass. STAGE –II: Charge toluene, sodium hydride and Stage I compound into the reactor. Cool the mass to 0- 5°C. Add ethyl 4-chloro acetoacetate into the reactor maintaining the temperature of the reaction mass at 0-5°C. After completion of the reaction, charge diluted hydrochloric acid and sodium chloride. Filter the mass and distil off toluene about 50% of volume and cool the mass slowly to 10-15°C. Centrifuge the mass and wash with toluene. STAGE –III: Charge hexane and pyridine in the reactor, heat the reaction mass to 50°C. Add orthochlorobenzaldehyde into the reactor for 4 to 5 hours at 50-55°C. Maintain the mass for 4 hours and distil off hexane completely below 55°C. Cool the mass and charge toluene into the reactor followed by acetic acid. Charge stage-II compound into the reactor and maintain for 4 hours at room temperature. After completion of the reaction, Charge water into the reactor and stir. Discard the bottom aqueous layer to ETP. Distil off toluene completely under vacuum below 85°C. Cool the mass and charge ethyl acetate. Stir and cool the mass to 0-5°C. Centrifuge the material and wash with ethyl acetate. Stage – IV: Charge hexane, Stage III compound and Stage-1A compound into the reactor. Heat the reaction mass to reflux and maintain for 4 hours. Cool the mass to 25-30°C. Centrifuge the material and wash with hexane. Stage V: Charge monomethyl amine and Stage IV material into a reactor and heat to 75-80°C. After completion of the reaction, cool the mass to room temperature. Centrifuge the material to produce Amlodipine Base compound. STAGE –VI: Charge methanol, Amlodipine Base compound into a reactor and add Benzene sulphonic acid slowly for 3-4 hours at 45-50°C. After completion of reaction, distil off methanol completely. Charge ethyl acetate into the reactor and cool to 0-5°C. Centrifuge the material and wash with water followed by ethyl acetate. Dry the material at 50-55°C to give Amlodipinbesylate.

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Route of Synthesis:

Page 82 of 179

Material Balance:

Stage -I INPUT QTY.(KGS) OUTPUT QTY.(KGS) Phthalic anhydride 100 Stage -I 100 Monoethanol amine 45 Solv Rec (Toluene) 190 Toluene 196 Residue 25 Purified Water 200 Solvent loss 6 Effluent 220 Total 54 1 Total 54 1

Stage-1A INPUT QTY.(KGS ) OUTPUT QTY.(KGS) Methyl aceto acetate 40 Stage 1A 35 Liq ammonia 96 Aq. Effluent 111 Total 146 Total 146

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Stage -II INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage I 100 Stage -II 125 Ethyl Chloroaceto acetate 55 Solv Rec (Toluene) 210 Hcl 5 Residue 131 Acetic acid 18 Solvent loss 5 Sodium chloride 50 Sodium hydride 28 Toluene 215 Total 471 Total 471

Stage-III INPUT QTY.(KGS) OUTPUT QTY.(KGS) Ortho Chlorobenzaldehyde 40 Stage III 150 Hexane 191 Sol. Rec (Tol) 488 Piperidine 2 Sol Rec.(EA) 343 Acetic acid 25 Sol Rec. (Hex) 183 Toluene 500 Aq. Effiuent 147 Purified Water 130 Residue 25 Stage II 125 Solvent loss 27 Ethyl acetate 350 Total 1413 Total 1413

Stage-IV INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage -III 150 Stage IV 150 Stage -IA 35 Sol Rec (Hex) 342 Hexane 356 Residue 35 Solvent loss 14 Total 541 Total 541 Stage-V INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage IV 150 Stage V 100 MMA 175 Aq. Effluent 225 Total 325 Total 325

Stage-VI INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage V 100 Stage VI 100 Benzene Sulfonic acid 64 Sol. Rec(MeOH) 195 Methanol 200 Sol. Rec (EA) 243 Ethyl acetate 250 Aq. Effiuent 144 Purified water 100 Residue 20 Solvent loss 12 Total 714 Total 714

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32. Amlodipine base

Page 85 of 179

Route of synthesis:

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Material Balance:

Stage-I INPUT QTY.(KGS) OUTPUT QTY.(KGS) Phthalic anhydride 100 Stage -I 100 Monoethanol amine 45 Solv Rec (Toluene) 190 Toluene 196 Residue 25 Purified Water 150 Solvent loss 6 Effluent 170 Total 491 Total 491

Stage-1A INPUT QTY.(KGS) OUTPUT QTY.(KGS) Methyl aceto acetate 40 Stage 1A 35 Liq ammonia 96 Aq. Effluent 111 Total 146 Total 146

Stage -II INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage I 100 Stage -II 125 Ethyl Chloroaceto acetate 55 Sol v Rec (Toluene) 210 Hcl 5 Residue 131 Acetic acid 18 Solvent loss 5 Sodium chloride 50 Sodium hydride 28 Toluene 215 Total 471 Total 471

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Stage -III INPUT QTY.(KGS) OUTPUT QTY.(KGS) Ortho Chlorobenzaldehyde 40 Stage III 150 Hexane 191 Sol. Rec (Tol) 488 Piperidine 2 Sol Rec.(EA) 343 Acetic acid 25 Sol Rec. (Hex) 183 Toluene 500 Aq. Effl uent 167 Purified Water 150 Residue 25 Stage II 125 Solvent loss 27 Ethyl acetate 350 Total 1383 Total 1383

Stage -IV INPUT QTY.(KGS) OUTPUT QTY.(K GS) Stage -III 150 Stage IV 150 Stage -IA 35 Sol Rec (Hex) 342 Hexane 356 Residue 35 Solvent loss 14 Total 541 Total 541 Stage -V INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage IV 150 Stage V 100 MMA 275 Aq. Effluent 325 Total 425 Total 425

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33. 2,4-dihydro-4-[(4-(4-hydroxyphenyl)-1-piperazinyl)phenyl]-2-(1- methylpropyl)-3h-1,2,4-triazole-3-one

Process Description: Stage-I: Charge dimethyl formamide, potassium carbonate and 1-(4-Methyxy) piperadine into a reactor. Heat the mass to 60-65°C. Add paranitrochlorobenzene for 3-4 hours at same temperature. After completion of the reaction distil off dimethyl formamide completely. Cool the mass and charge methanol and carbon into the reaction. Maintain the mass for 30 min at 50-55°C and filter into another reactor. Cool the filtrate to 10-15°C and centrifuge. Wash the material in water. Slurry wash the cake with acetone to produce 1-(4- Methoxyphenyl)-1-(4-nitrophenyl) piperazine. Stage-II: Charge DMF, palladium carbon and 1-(4-Methoxyphenyl)-1-(4-nitrophenyl) piperazine into the reactor. Heat the mass to 50-55°C. Pass hydrogen gas for 18 hours. After completion of the reaction, cool the mass below 35°C and filter the mass. Cool the filtrate to 0-5°C and maintain. Centrifuge the mass to produce 1-(4-Methoxyphenyl)-1-(4-aminophenyl) piperazine. Stage-III + IV: Charge Methylene chloride and 1-(4-Methoxyphenyl)-1-(4-aminophenyl) piperazine compound into a reactor. Heat the mass to 35-45°C. Add phenyl chloroformate for 5-6 hours at same temperature. After completion of the reaction, charge water into the reactor. Separate the layers. Discard aqueous layer and charge organic layer. Distill off Methylene chloride completely and charge n-butanol into the reactor. Heat the mass to 55-60°C. Add hydrazine hydrate into the reactor. Maintain for 4 hours at same temperature and cool the mass. Centrifuge the mass and wash with n-butanol to produce 2,4-Dihydro-4-[(4- methoxyphenyl)-1-piperazinyl]phenyl hydrazine carboxamide. Stage-V: Charge DMF and carboxamide compound into the reactor and heat to 70-75°C. Add formanidineacetate into the reactor slowly. After completion of the reaction, cool the mass and centrifuge, to produce 2,4-Dihydro-4-[4-[(4-methoxyphenyl)-1-piperazinyl phenyl]-3H- 1,2,4-triazole-3-one. Stage-VI: Charge 2-bromobutane, potassium carbonate and triazole compound into a reactor. Heat to reflux and maintain for 8 hours. After completion of reaction filter the mass and distil off 2- bromebutane completely. Charge DMF into the reactor and acidify the mass with hydrochloric acid. Centrifuge the material and wash with DMF to produce 2,4-Dihydro-4-[4- [(4- methoxyphenyl)-1-piperazinyl phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazole-3-one. Stage-VII: Charge hydrobromic acid and stage-VI compound into a reactor and heat the mass to reflux. After completion of the reaction, distil off HBr completely and charge water into the reactor. Neutralize the mass with soda ash. Centrifuge the mass and wash with water to produce 2,4- Dihydro-4-[4-[(4-hydroxyphenyl)-1-piperazinyl] phenyl]-2-(1-methylpropyl)-3H-1,2,4- triazole-3-one (ITR-INT-B).

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Route of Synthesis:

Page 90 of 179

Mass Balance:

Stage -01 Int -B INPUT QTY.(KGS) OUTPUT QTY.(KGS) 1-(4 -Methyxy) piperadine 86.9 Stage -I 132.4 Paranitrochlorobenzene 71.2 Solvent Rec (Methanol) 198.9 Pot assium carbonate 77.1 Solvent Rec (Acetone) 200.2 Dimethyl formamide 101.5 Solvent Rec (DMF) 98.1 Methanol 203.3 Aq. Effluent 176.5 Acetone 205.7 Spent carbon 3.5 Carbon 1.7 Residue 54.8 Water 130.3 Solvent loss 13.3 Total 877.7 Total 877.7

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Stage-02 Int-B INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage -I 132.4 Stage -II 118.3 Dimethyl formamide 238.4 Solvent Rec (DMF) 231.4 Palladium carbon 0.1 Gas loss 5.0 Hydrogen gas 10 Residue 19.2 Solvent loss 7.0 Total 380.9 Total 380.9

Stage -03 -04 Int -B INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage -II 118.3 Stage -IV 136.0 Phenyl chloroformate 78.6 Solvent Rec (MDC) 240.0 Sodium bicarbonate 71.0 Solvent Rec (Butanol) 145.2 Methylene chloride 246.0 Aq. Effluent 220 .8 Hydragin hydrate 65.0 Residue 41.8 n-Bu tanol 147.8 Water 65 .7 Solvent loss 8.6 Total 792 .4 Total 792 .4

Stage -05 Int -B INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage -IV 136.0 Stage -V 121.2 Formamidine acetate 63.6 Solvent Rec (DMF) 380.3 Dimethyl formamide 390.0 Residue 78.3 Solvent loss 9.7 Total 589.5 Total 589.5

Stage -06 Int -B INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage -V 121.2 Stage -VI 92.9 2-Bromo butane 125.2 Solvent Rec (DMF) 349.7 Potassium carbonate 51.0 Solvent Rec (2 -BB) 92.0 Dimethyl formamide 357.1 Residue 148.8 Hydrochl oric acid 38.4 Solvent loss 9.4 Total 692.8 Total 692.8

Stage-07 Int-B INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage -VI 92.9 ITR -INT -B 78.0 Hydrobromic acid 961.9 Hydrobromic acid rec 935.5 Soda ash 86.7 Aq. Effluent 217 .6 Water 100 .0 Solvent loss 10.4 Total 1241.5 Total 1241.5

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34. Metoprolol Tartrate

Process Description: Water take in Reactor add Epichlorohydrine and charge in 4.Methoxy Ethyl Phynol Maintain and add Caustic soda solution reaction in 7 hours and water wash and distill it. Product unload in HDPE Carboys. Metoprolol Base take into Ethyl acetate and Methanol and a solution of Tartric acid in Methanol at 60-65oC in 4 hours reflux and cooling. Product centrifuge and wash with Ethyl Acetate. Finished product dry in FBD and packed in HDPE container.

Route of Synthesis:

Mass Balance:

Stage -I (Epoxide) INPUT QTY.(KGS) OUTPUT QTY.(KGS) 4MEP 100.00 Epoxide 126.00 Epichlorohydrine 100.00 Effluent 404.00 Caustic soda 30.00 Water 300.00 Total 530.00 Total 530.00

STAGE-2 (Metoprolol Base) INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage -1 126.00 Metoprolol Base 149.00 MIPA 300.00 Effluent 767 .00 Water 400 .00 Toluene Reco 260.00 Toluene 400.00 Solvent loss 140.00 HCL 60.00 Caustic lye 30.00 Total 1316 .00 Total 1316 .00

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STAGE -3 (Metoprolol Tartrate) INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage -2 100.00 Metoprolol Tartrate 118.00 Ehtyl Acetate 600.00 Ethyl acetate reco 540.00 Tartric Acid 25.00 Methanol reco 315.00 Methanol 350.00 Solvent loss 95.00 Dry loss 7.00 Total 1075.0 0 Total 1075.00

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35. 1-(Isopropylamino)-3-[4-(2-methoxyethyl) phenoxy]-2-propanol

Route of Synthesis:

Mass Balance:

STAGE -1 (Epoxide) INPUT QTY.(KGS) OUTPUT QTY.(KGS) 4MEP 100.00 Epoxide 126.00 Epichlorohydrine 100.00 Effluent 404.00 Caustic soda 30.00 Water 300.00 Tota l 530.00 Total 530.00

STAGE -2 (Metoprolol Base) INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage -1 126.00 Metoprolol Base 149.00 MIPA 300.00 Effluent 718 .00 Water 351.00 Toluene Reco 260.00 Toluene 400.00 Solvent loss 140.00 HCL 60.00 Caustic lye 30.00 Total 1267.00 Total 1267.00

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36. Metoprolol Succinate

Process Description: Water take in Reactor add Epichlorohydrine and charge in 4.Methoxy Ethyl Phynol Maintain and add Caustic soda solution reaction in 7 hours and water wash and distill it. Product unload in HDPE Carboy’s. Metoprolol Base take into Ethyl acetate and Methanol and a solution of Succinic acid in Methanol at 60-65 oC in 4 hours reflux and cooling. Product centrifuge and wash with Ethyl Acetate. Finished product dry in FBD and packed in HDPE container.

Route of Synthesis:

Mass Balance:

STAGE -1 (Epoxide) INPUT QTY.(KGS) OUTPUT QTY.(KGS) 4MEP 100.00 Epoxide 126.00 Epichlorohydrine 100.00 Effluent 354 .00 Caustic soda 30.00 Water 250 .00 Total 480 .00 Total 480 .00

STAGE -2 (Me toprolol Base) INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage -1 126.00 Metoprolol Base 149.00 MIPA 300.00 Effluent 667 .00 Water 300 .00 Toluene Reco 260.00 Toluene 400.00 Solvent loss 140.00 HCL 60.00 Caustic lye 30.00 Total 1216 .00 Total 1216 .00

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STA GE -3 (Metoprolol Succinate) INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage -2 100.00 Metoprolol Succinate 112.00 Ehtyl Acetate 400.00 Effluent 75.00 Succinic Acid 21.00 EA Reco 360.00 Methanol 70.00 Solvent loss 40.00 Dry loss 4.00 Total 591.00 Total 591.0 0

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37. Ketoconazole

Process Description:

Stage-III: Cis-Tosylate (KT-II) is reacted with Para hydroxyl phenyl N-acetyl piperazine and sodium methoxide in the presence of dimethyl sulfoxide as solvent. After completion of the reaction, sodium hydroxide solution is charged into the reactor and maintained. The mass is centrifuged. The wet cake is treated with water and further by acetone. The wet cake is taken for next stage.

Stage IV: The wet cake is dissolved in ethyl acetate and methanol, and treated with carbon. The mass is filtered and the solution distilled off. The residue is cooled and centrifuged. The material is dried to produce Ketoconazole.

Route of Synthesis:

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Material Balance:

Stage-I Input QTY.(kgs) Output QTY.( kgs) CBB 780 Stage -1 450 IMD 693.3 IMD Rec 360 DMF 37.2 Toluene Rec 2207.0 Toluene 2275.5 Ethyle Acetate 1620.0 Sodium Bicarbonate 148.2 Aq. Effluent 15 99.4 Sodium hydroxide 120.0 Spent carbon 12.0 Water 705.0 Residue 130.0 HCl 156 Process loss 254 .9 Ethyl Acetate 1706.4 Activated Carbon 6.0 Vacuum Salt 6.0 Total 66 33.3 Total 66 33.3

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Stage -II Input QTY.(kgs) Output QTY.(kgs) Stage -1 450.0 Stage -2 600.0 Methylenechloride 3217.5 Methylenechloride Rec 3024.0 P-Toluene Sulfonyl Chl oride 465.0 Methanol Rec 1375.0 Sodium Carbonate 307.5 Aq. Effluent 778.0 HCl 12.0 Process Loss 400 Methanol 1425.0 Water 420 Total 6297.0 Total 6297.0

Stage -III Input QTY.(kgs) Output QTY.(kgs) Stage -2 600 Stage -3 650.0 PeraHydroxy phenyl n -acetyl piperazine 285.0 Dimethyl Solfoxide Rec 779.0 Dimethyl Solfoxide 847.0 Acetone Rec 300.0 Sodium methoxide powder 70.0 Aq. Effluent 408.0 Sodium Hydroxide 50.0 Residue 59.0 Acetone 240.0 Process loss 68.0 Methnol 7.0 Water 165.0 Total 2264 .0 Total 2264.0

Stage -IV Input QTY.(kgs) Output QTY.(kgs) Stage -3 650 Ketoconazole 510.0 Ethyl Acetate 2220.0 EA + Methanol Rec 2550.0 Methanol 464.0 Spent Carbon 40 Activated Carbon 20 Residue 80.0 Proess Loss 174.0 Total 3354.0 Total 3354.0

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38. Phthaloyl amlodipine

Process Description:

Stage I: Charge toluene, phthalic anhydride and mono-ethanol amine into the reactor. Heat the mass to reflux. Maintain for 4 hours at reflux. After completion of the reaction, cool the mass below 35°C and charge water. Stir the mass and settle for 1 hour. Discard bottom aqueous layer to ETP. Cool the mass to 10-15°C. Centrifuge the material and wash with toluene. STAGE –1A: Charge Methyl acetoacetate and ammonia solution into the reactor and maintain for 6 hours. Filter the mass. STAGE –II: Charge toluene, sodium hydride and Stage I compound into the reactor. Cool the mass to 0- 5°C. Add ethyl 4-chloro acetoacetate into the reactor maintaining the temperature of the reaction mass at 0-5°C. After completion of the reaction, charge diluted hydrochloric acid and sodium chloride. Filter the mass and distil off toluene about 50% of volume and cool the mass slowly to 10-15°C. Centrifuge the mass and wash with toluene. STAGE –III: Charge hexane and pyridine in the reactor, heat the reaction mass to 50°C. Add orthochlorobenzaldehyde into the reactor for 4 to 5 hours at 50-55°C. Maintain the mass for 4 hours and distil off hexane completely below 55°C. Cool the mass and charge toluene into the reactor followed by acetic acid. Charge stage-II compound into the reactor and maintain for 4 hours at room temperature. After completion of the reaction, Charge water into the reactor and stir. Discard the bottom aqueous layer to ETP. Distil off toluene completely under vacuum below 85°C. Cool the mass and charge ethyl acetate. Stir and cool the mass to 0-5°C. Centrifuge the material and wash with ethyl acetate. Stage – IV: Charge hexane, Stage III compound and Stage-1A compound into the reactor. Heat the reaction mass to reflux and maintain for 4 hours. Cool the mass to 25-30°C. Centrifuge the material and wash with hexane.

Route of Synthesis:

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Page 102 of 179

Material Balance:

Stage -I INPUT QTY.(KGS) OUTPUT QTY.(KGS) Phthalic anhydride 100 Stage -I 100 Monoethanol amine 45 Solv Re c (Toluene) 190 Toluene 196 Residue 25 Purified Water 250 Solvent loss 6 Effluent 270 Total 591 Total 591

Stage-1A INPUT QTY.(KGS) OUTPUT QTY.(KGS) Methyl aceto acetate 40 Stage 1A 35 Liq ammonia 96 Aq. Effluent 111 Total 146 Total 146

Stag e-II INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage I 100 Stage -II 125 Ethyl Chloroaceto acetate 55 Solv Rec (Toluene) 210 Hcl 5 Residue 131 Acetic acid 18 Solvent loss 5 Sodium chloride 50 Sodium hydride 28 Toluene 215 Total 471 Total 471

Stage-III INPUT QTY.(KGS) OUTPUT QTY.(KGS) Ortho Chlorobenzaldehyde 40 Stage III 150 Hexane 191 Sol. Rec (Tol) 488 Piperidine 2 Sol Rec.(EA) 343 Acetic acid 25 Sol Rec. (Hex) 183 Toluene 500 Aq. Effiuent 267 Purified Water 250 Residue 25 Stage II 125 Solv ent loss 27 Ethyl acetate 350 Total 1483 Total 1483

Stage-IV INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage -III 150 Stage IV 150 Stage -IA 35 Sol Rec (Hex) 342 Hexane 356 Residue 35 Solvent loss 14 Total 541 Total 541

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39. 2,4-Dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl] phenyl]-2-(1- methylpropyl)-3H-1,2,4-triazol-3-one

Process Description: Stage-I: Charge dimethyl formamide, potassium carbonate and 1-(4-Methyxy) piperadine into a reactor. Heat the mass to 60-65°C. Add paranitrochlorobenzene for 3-4 hours at same temperature. After completion of the reaction distil off dimethyl formamide completely. Cool the mass and charge methanol and carbon into the reaction. Maintain the mass for 30 min at 50-55°C and filter into another reactor. Cool the filtrate to 10-15°C and centrifuge. Wash the material in water. Slurry wash the cake with acetone to produce 1-(4- Methoxyphenyl)-1-(4-nitrophenyl) piperazine. Stage-II: Charge DMF, palladium carbon and 1-(4-Methoxyphenyl)-1-(4-nitrophenyl) piperazine into the reactor. Heat the mass to 50-55°C. Pass hydrogen gas for 18 hours. After completion of the reaction, cool the mass below 35°C and filter the mass. Cool the filtrate to 0-5°C and maintain. Centrifuge the mass to produce 1-(4-Methoxyphenyl)-1-(4-aminophenyl) piperazine Stage-III + IV: Charge Methylene chloride and 1-(4-Methoxyphenyl)-1-(4-aminophenyl) piperazine compound into a reactor. Heat the mass to 35-45°C. Add phenyl chloroformate for 5-6 hours at same temperature. After completion of the reaction, charge water into the reactor. Separate the layers. Discard aqueous layer and charge organic layer. Distill off Methylene chloride completely and charge n-butanol into the reactor. Heat the mass to 55-60°C. Add hydrazine hydrate into the reactor. Maintain for 4 hours at same temperature and cool the mass. Centrifuge the mass and wash with n-butanol to produce 2,4-Dihydro-4-[(4- methoxyphenyl)-1-piperazinyl]phenyl hydrazine carboxamide. Stage-V: Charge DMF and carboxamide compound into the reactor and heat to 70-75°C. Add formanidineacetate into the reactor slowly. After completion of the reaction, cool the mass and centrifuge, to produce 2,4-Dihydro-4-[4-[(4-methoxyphenyl)-1-piperazinyl phenyl]-3H- 1,2,4-triazole-3-one Stage-VI: Charge 2-bromobutane, potassium carbonate and triazole compound into a reactor. Heat to reflux and maintain for 8 hours. After completion of reaction filter the mass and distil off 2- bromebutane completely. Charge DMF into the reactor and acidify the mass with hydrochloric acid. Centrifuge the material and wash with DMF to produce 2,4-Dihydro-4-[4- [(4- methoxyphenyl)-1-piperazinyl phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazole-3-one.

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Route of Synthesis:

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Mass Balance:

Stage-01 Int-B INPUT QTY.(KGS) OUTPUT QTY.(KGS) 1-(4 -Meth yxy) piperadine 86.9 Stage -I 132.4 Paranitrochlorobenzene 71.2 Solvent Rec (Methanol) 198.9 Potassium carbonate 77.1 Solvent Rec (Acetone) 200.2 Dimethyl formamide 101.5 Solvent Rec (DMF) 98.1 Methanol 203.3 Aq. Effluent 176.5 Acetone 205.7 Spent carb on 3.5 Carbon 1.7 Residue 54.8 Water 130.3 Solvent loss 13.3 Total 877.7 Total 877.7

Stage -02 Int -B INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage -I 132.4 Stage -II 118.3 Dimethyl formamide 238.4 Solvent Rec (DMF) 231.4 Palladium carbon 0.1 Gas loss 5.0 Hydrogen gas 10 Residue 19.2 Solvent loss 7.0 Total 380.9 Total 380.9

Stage-03-04 Int-B INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage -II 118.3 Stage -IV 136.0 Phenyl chloroformate 78.6 Solvent Rec (MDC) 240.0 Sodium bicarbonate 71.0 Solvent Rec (Butan ol) 145.2 Methylene chloride 246.0 Aq. Effluent 350.8 Hydragin hydrate 65.0 Residue 41.8 n-Butanol 147.8 Water 195.7 Solvent loss 8.6 Total 922.4 Total 922.4

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Stage -05 Int -B INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage -IV 136.0 Stage -V 121.2 Formam idine acetate 63.6 Solvent Rec (DMF) 380.3 Dimethyl formamide 390.0 Residue 78.3 Solvent loss 9.7 Total 589.5 Total 589.5

Stage -06 Int -B INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage -V 121.2 Stage -VI 92.9 2-Bromo butane 125.2 Solvent Rec (DMF) 349.7 Potassium carbonate 51.0 Solvent Rec (2 -BB) 92.0 Dimethyl formamide 357.1 Residue 148.8 Hydrochloric acid 38.4 Solvent loss 9.4 Total 692.8 Total 692.8

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GROUP – III

40. Montelukast Sodium

Process Description: Stage-I: 1-(Hydoxy methyl) cyclo propane Acetonitrile (MEC-4) is reacted with methane sulfonyl chloride in presence of Diisoprpylethyl amine, and the product is further treated with Thiol acetic acid to give MAN. Stage-II: Condensation of MAN and (2-(2-(3(S)-(3-(2-(7-Chloro-2-quinolinyl) ethenyl) phenyl-3- (methane sulfonyloxy) propyl)-2-propanol) (QUID-8) in the presence with n-butyl lithium in the presence of toluene and Dimethyl foramide which on further hydrolysis with Caustic lye to give MOK-1 –Nitrile Stage-III: MOK-1 Nitrile underwent sodium hydroxide hydrolysis in the presence of toluene to give MOK-1. Stage-IV: MOK-1 treated with t-butyl amine protection with acetone acid to give MOK-2 butyl amine. Stage- V: MOK-2 t-butylamine on further treatment with caustic flakes to give sodium Montelukast (MOK-3). On further carbon purification with methanol to give Pure MK-3 salt (Montelukast Sodium).

Route of Synthesis:

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Mass Balance:

Stage -I Input Qty.(KGS) Output Qty.(kgs) N-vinyl pyrrolidone 108.1 Stage -I 96.5 Thiol acetic acid 74 Acetic acid 45.6 Diisopropyl ethylamine 6 Toluene recovered 1447.5 Toluene 1500 Toluene loss 7.5 Water 1000 Toluene residue 45 Methane sulfonyl Chloride 15 N-vinyl pyrrolidone 23.7 Thiol acetic acid 16.3 Diisopropyl ethylamine 6 Methane sul fonyl chloride 15 Water 1000 Total 27 03.1 Total 27 03.1

Stage-II Input QTY.(kgs) Output QTY.(kgs) Stage -I 96.5 Stage -II 350.6 Water generated during Thiophene -2-ethylamine 347.4 reaction 11.1 Toluene 2000 Toluene recovered 1940 Water 600 Toluene loss 10 Acetic acid 10 Toluene residue 50 Sodium chloride 50 Stage -I 17.9 Carbon 5 Thiophene -2-ethylamine 64.3 Acetic acid 10 Carbon 5 Sodium chloride 50 Water 600 Total 3108.9 Total 3108.9

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Stage -III Input QTY.(kgs) Output QTY.(kgs) Stage-III (Crude Nateglinide Form St age -II 350.6 H) 235.6 Sodium hydroxide 24.7 Sodium methoxide 21.7 Methanol 1219.8 Ammonia 6.8 Toluene 1700 Methanol recovered 1152 Water 800 Methanol loss 6 Acetic acid 30 Methanol wastewater 12 Sodium chloride 70 Me thanol residue 30 HCl for NaOH neutralization 7.9 Toluene recovered 1632 Toluene loss 6.8 Toluene residue 61.2 Stage -II 122.7 Methanol 6.9 Acetic acid 30 Sodium hydroxide 8.7 Sodium chloride 70 Water 784 NaCl from NaOH neutraliz ation 12.7 Water from NaOH neutralization 3.9 Total 4203 Total 4203

Stage -IV Input QTY.(kgs) Output QTY.(kgs) Stage -III 235.6 Stage -IV 198.7 Tertiary butyl amine 29.4 Acetone recovered 1536 Acetone 1600 Acetone loss 7.2 Toluene 2000 Acetone re sidue 56.8 Carbon 5 Toluene recovered 1920 Toluene loss 10 Toluene residue 70 Stage -III 58.9 Tertiary butyl amine 7.4 Carbon 5 Total 3870 Total 3870

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Stage -V Input QTY.(kgs) Output QTY.(kgs) Stage -IV 198.7 Montelukast Sodium 15 0 Sodium hydroxide 62.1 Tert -butylamine 18 Mdc 1800 Water generated during reaction 4.4 Acetic acid 25 MDC recovered 1737 Water 1000 MDC loss 9 Methanol 1000 MDC residue 54 Carbon 5 Methanol recovered 970 HCl for NaOH neutralization 47.6 Methanol lo ss 4 Methanol residue 26 Stage - IV 36.1 Acetic acid 25 Carbon 5 Sodium hydroxide 52.2 Water 947.9 NaCl from NaOH neutralization 76.3 Water from NaOH neutralization 23.5 Total 4138.4 Total 4138.4

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41. Valsartan

Process Description: Stage-1: L-Valine reacts with Methanol in presence of Methanol as solvent media to give Stage-1 as product. Stage-2: Stage-1 product reacts with 4-Bromomethyl-biphenyl-2-carbonitrile in presence of Methanol as solvent media to give Stage-2 as product. Stage-3: Stage-2 product reacts with Valeryl chloride in presence of Methanol as solvent media to give Stage-3 as product. Stage-4: Stage-3 product reacts with Sodium azide; Tri butyl tin chloride undergoes Hydrogenation in presence of Methanol as solvent media give Valsartan as product.

Route of Synthesis:

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Mass Balance:

Stage -I Input QTY.(kgs) Output QTY.(kgs) L-Valine 45.00 Stage -1 50.00 Thionyl Chloride 45.70 Methanol Rec. 758.00 Methanol 800.00 Toluene Rec. 474.00 Toluene 500.00 Orga nic Residue 8.33 Solvent Loss 65.00 Process Loss 35.37 Total 1390.70 Total 1390.70

Stage -II Input QTY.(kgs) Output QTY.(kgs) Stage -1 50.00 Stage -2 90.00 4-Bromomethyl -biphenyl -2- carbonitrile 82.00 Toluene Rec. 565.00 Potassium carbonate 45.00 Effluent Water 569.78 Toluene 600.00 Organic Residue 9.22 Water 500.00 Process Loss 13.00 Solvent Loss 30.00 Total 1277.00 Total 1277.00

Stage-III Input QTY.(kgs) Output QTY.(kgs) Stage -2 90.00 Stage -3 100.00 Valeryl Chloride 34.00 Toluene Rec. 660.00 Toluene 700.00 Effluent Water 444.80 TEA 20.00 Inorganic Solid Waste 10.00 Water 500.00 Organic Residue 16.93 Process Loss 12.27 Solvent Loss 35.00 Total 1279.00 Total 1279.00

Stage -IV Input QTY.(kgs) Output QTY.(KGS) Stage -3 100.00 Va lsartan 100.00 Sodium Azide 16.00 Toluene Rec. 660.00 Tri Butyl tin Chloride 80.00 MDC Rec. 475.00 Hydrogen Gas 0.50 Xylene Rec. 228.00 Sodium Hydroxide 20.00 N-Hexane Rec. 190.00 Xylene 240.00 Effluent Water 577.30 Toluene 700.00 Spent Carbon 10.00 Water 500.00 Organic Residue 9.22 Solvent Loss 82.00 Total 2406.50 Total 2406.50

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42. Venlafaxine Hydrochloride

Process Description: Anisole reacts with Aluminium chloride and acetyl chloride in methylene chloride togive 4- methoxy acetophene and 4-methoxy acetophenone reacts with dimethylformamide, sodium acetate and sulfur to give thioacetamide reacts with Cyclohexanone in presence of grignard reagent togive N,N Dimethyl-2-(1-hydroxy cycloridehexahydrate, in methanol to give N,N Dimethyl-2-(4-methoxyphenyl)ethyl amine which reacts with Borohydride and nickel chloride hexahydrate, in methanol to give N,N Dimethyl-2- (1-hydroxycyclohexyl)-2-(4-methoxyphenyl)ethyineor(+/-) 1-(2- Dimethylamino)-1-(4- methoxyphenyl)ethyl) cyclohexanol, which further crystallized in hydrochloride formation inisopropanol HCL and ethyl acetate as solvent to give final product Venlafaxine hydrochloride.

Route of Synthesis:

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Mass Balance:

Stage -I Input QTY.(kgs) Output QTY.(kgs) 4-Methoxy Benzoyl Cyanide 96.56 Stage -1 136.00 Methanol 349.52 Aqu Effluent 752.48 Sodium Methoxide 91.12 CFML 1957.04 Cyclohexanone 89.76 Toluene Reco 432.97 Toluene 481.08 Solvent Loss 48.11 Water 2228.08 Dry Loss 9.52 Total 3336.12 Total 33 36.12

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Stage -II Input QTY. (kgs) Output QTY.(kgs) Acetic Acid 815.00 Venafaxine Hydrochloride 100.00 Stage -1 136.00 Catalyst 5.00 Catalyst 5.00 Acetic Acid reco 773.00 Caustic soda 477.00 Reco loss 42.00 Formic soda 194.00 Aqu effluent 1457.00 Formaldehyde 112.00 Sodium sulpha te 27.00 Hydrochloric acid 251.00 Hyflo 4.00 Ethyl acetate 2253.00 Carbon 1.00 Sodium Sulphate 27.00 Ethyl Acetate Reco 2139.00 Sodium chloride 34.00 Reco loss 114.00 Hyflo 4.00 IPML 1550.00 IPA 1460.00 Dry Loss 18.00 IPA HCL 109.00 Activated Cha rcoal 1.00 Water 352.00 Total 6230.00 Total 6230.00

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43. Levocetirizine Dihydrochloride

Process Description: Stage-I: 1-[(4-Chlorophenyl) phenyl methyl]-4-[(phenyl sulphonyl] piperazine is deprotectedwith 4- Hydroxy benzoic acid in Hydro bromic acid then is condensed with 2(2- Chloroethoxyacetamide) in presence of Sodium carbonate in toluene and is reacted with sodium hydroxide and Hydrochloric Acid in acetone to give Levocetrizine Di hydrochloride as product.

Route of Synthesis:

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Mass Balance:

Stage -I INPUT QTY.(KGS) OUTPUT QTY.(KGS) 1-[((4 Chlorophenyl)phenyl)methyl] - 46.20 LevocetirizineDihydrochloride 50 4-[(phenylsulphonyl)]piperazine Recovery Toluene 1440 2(2-Chloroethoxy )acetamide 14.90 Recovery MDC 1767 4-Hydroxy benzoic acid 16 Recovery Acetone 442 Hydrobromic acid 8.80 Loss of Toluene 75 Sodium hydroxide 8.70 Loss of MDC 93 Hydrochloric acid 15.80 Loss of Toluene 23 Sodium carbonate 11.50 Activated Carbon 4 Potassium iodide 1.70 Effluent 1000.24 Toluene 1515 Residue 41.3 6 MDC 1860 Acetone 465 Activated carbon 4 Purified water 968 Total 4935.60 Total 4935.60

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44. Pregabalin

Process Description: Sodium Hydroxide solution in Process water is chilled at 0-10°C and then charge R-(-)-3- (Carbamoylmethyl)-5-methylhexanoic acid [R-(-)-CMH]. Addition of liquid Bromine is done at 0- 5°C then raise the temperature of the reaction mass up to 30-35°C. After reaction monitoring, raise the temperature of the reaction mass to 55-60°C and apply carbon treatment. The clear filtrate is then received in another reactor. Excess water is distilled off from the reaction mass. The reaction mixture is acidified with concentrated Hydrochloric acid. Reaction mass is then up to 80-85°C and after that gradual cooling to 25-30°C. The material is centrifuged after maintaining of the reaction mass at 25-30°C for 4-6 hrs. The dry material is then charged in IPA and raises the temperature to 80-85°C. Add DM water to reaction mass at 80-85°C. Filter the clear reaction mass and chill it to 8-12°C. The material is then centrifuged and dried in under vacuum.

Route of Synthesis:

Mass Balance:

Stage-1 Input QTY.(kgs) Output QTY.(kgs) Sodium Hydroxide 347.2 Stage -1 162.5 4-CMH 250.00 Spent carbon and hyflo 28.00 Liquid Bromine 224.00 Spent ML 2623.7 Hyflo 12.50 Loss on drying 62.5 Activated carbon 3.00 Hydrochloric acid 450.00 Process water 1590.00 Total 2877.00 Total 2877.00

Stage-2 Input QTY.(kgs) Output QTY.(kgs) Stage -1 215.00 Pregabalin 182.8 IPA 1290.00 Spent ML 1750.00 DM water 460.00 Loss on drying 32.2 Total 1965.00 Total 1965.00

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45. Veratric Acid

Process Description: Stage -I: Catechol is methylated by Dimethyl sulphate in presence of aqueous alkaline solution and gives Veratrol (Veratric acid Stage-I) as an organic layer.

Stage II: Veratric acid Stage-I (Veratrol) is acylated with Acetyl chloride in presence of anhydrous aluminum chloride in Methylene dichloride solvent. Reaction mass is quenched in chilled Hydrochloric acid solution to get Veratric acid Stage-II.

Stage III: Veratric acid Stage-II (Acetyl Veratrol) is oxidized with Sodium hypochlorite and further it is hydrolysed by Hydrochloric acid to give Veratric acid. Isolate solid by centrifugation and dry it.

Route of Synthesis:

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Mass Balance:

Stage-I INPUT QTY.(KGS) OUTPUT QTY.(KGS) Catechol 350 Stage-I 400 Dimethyl Sulphate 875 Effluent 1782 Sodium hydroxide 288 Salt 6 Purified water 695 Guicol 20 Total 2208 Total 2208

Stage-II INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage-I 400 Stage-II 445 Methylene dichloride 1680 Recovery Methylene Dichloride 1440 Aluminium chloride 500 Loss of Methylene Dichloride 240 Acetyl chloride 395 Poly Aluminium chloride 3300 Hydrochloric Acid 240 Sodium Bicarbonate 10 Purified water 2200 Total 5425 Total 5425

Stage-III INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage-II 445 Veratric Acid 380 Methylene dichloride 500 Recovery Methylene Dichloride 440 Sodium Hypo Chlorite 4675 Loss of Methylene Dichloride 60 Activated Carbon 10 Residue 15 Hydrochloric Acid 1120 Effluent 6875 Sodium meta bi sulphate 30 Activated Carbon 10 Purified Water 1000 Total 7780 Total 7780

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46. Fluconazole

Process Description: Stage-I: Charge Methylene dichloride and aluminium chloride into the reactor. Cool the mass to below 5°C. Charge 1,3-Difluorobenzene into the reactor. Add slowly chloroacetyl chloride into the reactor for 4 to 5 hours below 10°C. Charge the reaction mass to ice and hydrochloric acid. Stir the reaction mass for 4 hours and separate the layers. Distil off MDC completely below 50°C. Charge isopropyl alcohol and 4-amino-1,2,4-triazole into the reactor and maintain for 6 hours at 45-50°C. Cool the reaction mass to 10°C and centrifuge material and dry to produce 2-(1H-1,2,4-triazole-1-yl)-2’,4’-difluoroacetophenone salt. Stage-II: Charge water, sodium nitrite and 2-(1H-1,2,4-triazole-1-yl)-2’,4’-difluoroacetophenone into the reactor and heat to 50-60°C. Slowly add hydrochloric acid at 50-60°C and maintain for 12 hours. Cool the mass below 20°C and neutralize the reaction mass with ammonia solution. Centrifuge the mass and wash with water. Dry the material to produce 1-(2,4- difluorophenyl)- 2-(1H,1,2,4-Triazol-1-yl) ethanone. Stage-III: Charge Toluene, 1-(2,4-difluorophenyl)- 2-(1H,1,2,4-Triazol-1-yl) ethanone, potassium hydroxide, 1,2,4,-Triazole and Trimethylsulphoxinium iodide into the reactor. Heat to reflux and maintain for 12 hours.Distil off Toluene completely. Cool the reaction mass and charge water into the reactor. Charge toluene into the reactor and stir for 30 minutes. Settle the mass for 30 minutes. Separate the layers. Discard the bottom aqueous layer. Cool the mass to 10°C and centrifuge. Dry the material to produce Fluconazole crude. Charge water, crude and ammonia solution into the reactor. Check complete dissolution and charge carbon. Stir for 30 min and filter over hyflow bed. Charge toluene and citric acid. Neutralize the mass with hydrochloric acid. Stir for30 minutes and settle for 30 minutes. Separate the layers and discard aqueous layer. Cool the mass. Centrifuge the mass and wash with toluene. Dry the material to produce Fluconazole pharma.

Route of Synthesis:

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Material Balance:

Stage-I Input QTY.(KGS) Output QTY.(KGS) 1,3 -Difluorobenzene 200 Stage -I Compound 480 Aluminium Chloride 240 Sol Rec(MDC) 1050 Methylene Chloride 1200 Sol Rec (IPA) 740 Chloroacetyl chloride 210 AlCl3 gel for Rec. 1100 4-Amino -1,2,4 -Triazole 162 Aq. Effluent 490 IPA 790 Residue 30 Sodium bicarbonate 15 Solvent loss 202 Hydrochloric acid 75 Ice & Water 1200 Total 4092 Total 4092

Stage-II Input QTY.(KGS) Output QTY.(KGS) Stage -I Compound 480 Stage -II 370 Sodium Nitrite 118 Aq. Effluent 1778 Hydrochloric acid 250 Water 1100 Ammonia Solution 200 Total 2148 Total 2148

Stage -III Input QTY.(KGS) Output QTY.(KGS) Stage -II 370 Stage -III 370 TrimethylSulphoxoniumIodiade 330 Sol Rec (Toluene) 550 1,2,4 -Triazole 165 Aq. Effluent 1170 Potassium Hydroxide 235 Residue 50 Toluene 600 Solvent loss 60 Water 500 Total 2200 Total 2200

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Stage -IV Input QTY.(KGS) Output QTY.(KGS) Stage -III 370 Fluconazole 250 Toluene 1500 Solvent Reco (Tol) 1428 Activated carbon 15 Aq. Effuient 1478 Citric Acid 15 Spen t Carbon 30 Ammonia solution 640 Spent hyflow 24 Hydrochloric Acid 180 Residue 50 Hyflowsupercell 12 Solvent loss 72 Water 600 Total 3332 Total 3332

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47. Itraconazole

Process Description: Stage-I: charge dimethyl formamide, cis-2[bromomethyl-2-(2,4 dichlorophenyl)1,3 dioxalane-4- yl)methyl benzoate and 1H-1,2,4 triazole into a reactor. Charge sodium hydroxide solution into the reactor.Heat to reflux and maintain for 8 hours. After completion of reaction, cool the mass below 35°C and charge potassium carbonate. Stir the mass for 30 minutes and filter. Charge the filtrate and distil off DMF completely. Charge water and toluene into the reactor and stir for 30 minutes. Discard the bottom aqueous layer to ETP. Cool the organic layer to 10-15°C. Centrifuge the material and wash with toluene. Dry the material at 60-65°C to produce Cis-[2- (2,4-dichlorophenyl)-2-(1H,1,2,4-triazol-1yl methyl)1,3 dioxolan- 4yl]methanol. Stage-II: Charge methylene dichloride, Step-I compound and triethyl amine into a reactor. Slowly add methane sulfonyl chloride into the reactor at 10-15°C. After completion of the reaction, charge water and stir for 30 minutes. Separate the layers. Charge organic layer in to the reactor and charge carbon. Stir for 30 minutes and filter the mass into another reactor. Add hydrochloric acid into the reactor at 25-30°C. Cool the mass to 10-15°C. Centrifuge and wash with methylene dichloride. Dry the material at 45-50°C to produce Cis-[2-(2, 4 - dichlorophenyl) - 2 - (1H,1, 2, 4 - triazol - 1yl- methyl) 1,3-dioxolan-4yl]-methyl methane sulfonate (ITR-INT-A). Process description–ITR-INT-B: Stage-I: Charge dimethyl formamide, potassium carbonate and 1-(4-Methyxy) piperadine into a reactor. Heat the mass to 60-65°C. Add paranitrochlorobenzene for 3-4 hours at same temperature. After completion of the reaction distil off dimethyl formamide completely. Cool the mass and charge methanol and carbon into the reaction. Maintain the mass for 30 min at 50-55°C and filter into another reactor. Cool the filtrate to 10-15°C and centrifuge. Wash the material in water. Slurry wash the cake with acetone to produce 1-(4- Methoxyphenyl)-1-(4-nitrophenyl) piperazine. Stage-II: Charge DMF, palladium carbon and 1-(4-Methoxyphenyl)-1-(4-nitrophenyl) piperazine into the reactor. Heat the mass to 50-55°C. Pass hydrogen gas for 18 hours. After completion of the reaction, cool the mass below 35°C and filter the mass. Cool the filtrate to 0-5°C and maintain. Centrifuge the mass to produce 1-(4-Methoxyphenyl)-1-(4-aminophenyl) piperazine. Stage-III + IV: Charge Methylene chloride and 1-(4-Methoxyphenyl)-1-(4-aminophenyl) piperazine compound into a reactor. Heat the mass to 35-45°C. Add phenyl chloroformate for 5-6 hours at same temperature. After completion of the reaction, charge water into the reactor. Separate the layers. Discard aqueous layer and charge organic layer. Distill off Methylene chloride completely and charge n-butanol into the reactor. Heat the mass to 55-60°C. Add hydrazine hydrate into the reactor. Maintain for 4 hours at same temperature and cool the mass. Centrifuge the mass and wash with n-butanol to produce 2,4-Dihydro-4-[(4-

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methoxyphenyl)-1-piperazinyl]phenyl hydrazine carboxamide. Stage-V: Charge DMF and carboxamide compound into the reactor and heat to 70-75°C. Add formanidineacetate into the reactor slowly. After completion of the reaction, cool the mass and centrifuge, to produce 2,4-Dihydro-4-[4-[(4-methoxyphenyl)-1-piperazinyl phenyl]-3H- 1,2,4-triazole-3-one Stage-VI: Charge 2-bromobutane, potassium carbonate and triazole compound into a reactor. Heat to reflux and maintain for 8 hours. After completion of reaction filter the mass and distil off 2- bromebutane completely. Charge DMF into the reactor and acidify the mass with hydrochloric acid. Centrifuge the material and wash with DMF to produce 2,4-Dihydro-4-[4- [(4- methoxyphenyl)-1-piperazinyl phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazole-3-one Stage-VII: Charge hydrobromic acid and stage-VI compound into a reactor and heat the mass to reflux. After completion of the reaction, distil off HBr completely and charge water into the reactor. Neutralize the mass with soda ash. Centrifuge the mass and wash with water to produce 2,4- Dihydro-4-[4-[(4-hydroxyphenyl)-1-piperazinyl] phenyl]-2-(1-methylpropyl)-3H-1,2,4- triazole-3-one (ITR-INT-B) ITRA-Stage-I/II/III: Charge water, potassium hydroxide, Cis-(2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxalane-4-yl) methyl methane sulfonate and 2,4-Dihydro-4-[4-[(4- hydroxyphenyl)-1-piperazinyl] phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazole-3-one into the reactor. Heat the mass to 80-85°C and maintain for 6 hrs. Cool the mass below 35°C and centrifuge. Charge the cake and DMF into a reactor and maintain for 1 hour at room temperature. Centrifuge the mass and wash with DMF to produce Itraconazole crude. The crude is treated with toluene, methanoland ethyl acetate and carbon to produce Itraconazole pure.

Route of Synthesis:

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Material Balance:

Stage -01 Int -A INPUT QTY.(KGS) OUTPUT QTY.(KGS) Cis -Bromobenzoate 111.3 Triazole derivative 95.8 1H,1,2,4 -Triazole 70.4 Solvent rec (DMF) 181.7 Potassium carbonate 105.7 Solvent rec (Tol) 153.3 Dimethyl formamide 186.7 Aq. Effluent 324.3 Sodium hydroxide 10.6 Residue 64.5 Toluene 157.4 Solvent loss 9.1 Water 186.7 Total 828.7 Total 828.7

Stage-02 Int-A INPUT QTY.(KGS) OUTPUT QTY.(KGS) Triazole derivative 95.8 ITR -INT -A 101.5 Triethyl amine 40.2 Solvent rec (MDC) 187.0 Methane sulfonyl chloride 38.3 Methylene chloride 193.8 Aq. Effluen t 192.0 Activated Carbon 3.8 Spent carbon 7.7 Sodium hydroxide 6.9 Residue 56.2 Water 172.4 Solvent loss 6.8 Total 551.2 Total 551.2

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Stage -01 Int -B INPUT QTY.(KGS) OUTPUT QTY.(KGS) 1-(4 -Methyxy) piperadine 86.9 Stage -I 132.4 Paranitrochlorobenz ene 71.2 Solvent Rec (Methanol) 198.9 Potassium carbonate 77.1 Solvent Rec (Acetone) 200.2 Dimethyl formamide 101.5 Solvent Rec (DMF) 98.1 Methanol 203.3 Aq. Effluent 176.5 Acetone 205.7 Spent carbon 3.5 Carbon 1.7 Residue 54.8 Water 130.3 Solvent lo ss 13.3 Total 877.7 Total 877.7

Stage -03 -04 Int -B INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage -II 118.3 Stage -IV 136.0 Phenyl chloroformate 78.6 Solvent Rec (MDC) 240.0 Sodium bicarbonate 71.0 Solvent Rec (Butanol) 145.2 Methylene chloride 246.0 Aq. Effluent 450.8 Hydragin hydrate 65.0 Residue 41.8 n-Butanol 147.8 Water 295.7 Solvent loss 8.6 Total 1022.4 Total 1022.4

Stage-05 Int-B INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage -IV 136.0 Stage -V 121.2 Formamidine acetate 63.6 Solvent Rec (DMF) 380.3 Dimethyl f ormamide 390.0 Residue 78.3 Solvent loss 9.7 Total 589.5 Total 589.5

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Hydrochloric acid 38.4 Solvent loss 9.4 Total 692.8 Total 692.8

Stage-07 Int-B INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage -VI 92.9 ITR -INT -B 78.0 Hydrobromic acid 961.9 Hydrobromic acid rec 935.5 Soda ash 86.7 Aq . Effluent 476.6 Water 359.0 Solvent loss 10.4 Total 692.8 Total 692.8

Stage-01 Intraconazole INPUT QTY.(KGS) OUTPUT QTY.(KGS) ITR -INT -A 101.5 IT -I 125.0 ITR -INT -B 78.0 Solvent Rec (DMF) 578.0 Water 287.5 Aq. Effluent 380.5 N,N -Dimethyl formamide 590 Residue 13.5 Potessium Hydroxide 52 Solvent loss 12.0 Total 1109 Total 1109 Stage-02 Itraconazole INPUT QTY.(KGS) OUTPUT QTY.(KGS) IT -I 125.0 Intraconazole 85.00 Toluene 165.0 Solvent Rec (Toluene) 160 Ethyle Acetate 432.0 Solvent Rec (EA) 420 Methanol 695.9 Solvent Rec (Methanol) 675 Carbon 2.3 Residue 34.1 HyflowSupercell 6.7 Spent Carbon 4.6 Spent Hyflow 10.3 Solvent Loss 37.9 Total 1426.9 Total 1426.9

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48. Cetirizine Dihydrochloride

Process Description: Stage-I: The 4-Chloro benzhydeylpiperazine react with 2-chloroethanol in presence of Triethylamine in toluene solvent. After reaction completion toluene was distilled under reduced pressure and added acetone and passed dry hydrogen chloride gas to isolate 4-Chloro benzhydrylpiperazineethoxy hydrochloride.

Stage-II: The 4-Chloro benzhydrylpiperazineethoxycompound react with Sodium monochloro acetate in presence of Potassium hydroxide in Dimethylformamide. After completion of reaction by adding water and adjust pH to 9.0 and extract with toluene. Again the aqueous layer is adjusted to pH 4.0 using Hydrogen chloride and the product is extracted with Methylene Dichloride. Distilled Methylene Dichloride, added acetone and passed dry Hydrogen chloride gas to isolate Cetirizine Dihydrochloride.

Route of Synthesis:

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Mass Balance:

Stage-I INPUT QTY.(KGS) OUTPUT QTY.(KGS) 4-Chloro benzhydeylpiperazine 230 Stage-I 240 Toluene 800 Recovery Toluene 752 2-Chloroethanol 115 Recovery Triethylamine 232 Triethylamine 250 Loss of To luene 48 Sodium carbonate 100 Less of Triethylamine 18 Purified water 2300 Effluent 2448.25 Residue 25.32 Carbon dioxide 31.43 Total 3795 Total 3795

Stage-II INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage-I 240 Stage-II 250 Sodium monochloro acetate 175 Recovery Toluene 1175 Potassium hydroxide 85 Recovery Methylene dichloride 690 Dimethylformamide 50 Recovery Acetone 697 Toluene 1250 Loss of Toluene 75 Methylene dichloride 750 Loss of Methylene dichloride 60 Acetone 750 Loss of Acetone 53 Hydrogen chloride 130 Effluent 2073.27 Activated carbon 38 Residue 85.13 Purified water 750 Hydrogen chloride gas 21.6 Activated carbon 38 Total 5218 Total 5218

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49. Rebeprazol Sodium

Process Description: Stage-1: 2, 3-Lutidine is reacted with Hydrogen Peroxide in presence of Acetic Acid to give N- Oxide it further reacts with Nitration mixture (Nitric Acid + Sulfuric Acid) to give Stage-1. Stage-2: Stage-1 is reacted with 3-Methoxy-1-Propanol and Sodium Hydroxide to get Stage-2 Compound Stage-3: Stage-2 Compound is reacted with Acetic Anhydride, Sodium Hydroxide and Hydrochloric Acid to get Stage-3 Compound Stage-4: Stage-3 Compound is reacted with Thionyl Chloride in the presence of MDC Solvent media to get Stage-4 compound Stage-5: Stage-4 Compound is reacted with 2-Mercapto Benzimidazole, Sodium hydroxide in the presence of Toluene Solvent Media to get Stage-5 Compound Stage-6: Stage-5 Compound is reacted with Sodium Hypochlorite to get Rabeprazole Base Stage-7: Rabeprazole Base is reacted with Sodium hydroxide to get Rabeprazole Sodium

Route of Synthesis:

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Mass Balance:

STAGE -1 INPUT QTY.(KGS) OUTPUT QTY.(KGS) 2,3 Lutidine 46.00 Stage -1 65.00 Acetic acid 46.00 Spent acid 140.00 Hydrogen peroxide 33.00 Effluent 400.80 Nitric acid 30.00 Organic Residue 7.20 Sulfuric acid 108.00 Water 350.00 Total 613.00 Total 613.00

STAGE -2 INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage-1 65.00 Stage-2 80.00 3-Methoxy-1 –propanol 40.00 Toluene Reco 235.00 Acetic anhydride Sodium hydroxide 18.50 DMSO Reco 188.00 Toluene 250.00 Solvent loss 22.00 DMSO 200.00 Inorganic solid waste 29.70 Organic waste 11.80 Water generate 7.00 Total 573.50 Total 573.50

STAGE -3 INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage-2 80.00 Stage-3 90.00 Acetic anhydride 150.00 Toluene Reco 660.00 NaOH 20.00 Acetic anhydride Reco 107.00 HCL 20.00 Effluent 360.50 Toluene 700.00 Organic Residue 13.50 Water 300.00 Process loss 39.00 Total 1230.00 Total 1230.00

STAGE-4 INPUT QTY.( KGS) OUTPUT QTY.(KGS) Stage -3 90.00 Stage -4 80.00 Thionyl chloride 53.00 MDC Reco 710.00 Sodium sulphate 10.00 Solvent loss 37.00 Water 500.00 Organic waste 10.00 MDC 750.00 Organic Residue 16.30 Process loss 23.20 Total 1403.00 Total 1403.00

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STAGE -5 INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage-4 80.00 Stage-5 100.00 2-mercapto benzimidazole 53.00 Toluene Rec. 375.00 Sodium Hydroxide 15.00 Solvent Loss 20.00 Toluene 400.00 Effluent 329.70 Water 300.00 Organic Residue 23.30 Total 848.00 Total 848.00

STAGE -6 INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage -5 100.00 Stage -6 100.00 Sodium hypochlorite (8%) 327.00 MDC Rec. 570.00 MDC 600.00 Acetone Rec. 137.00 Acetone 150.00 Effluent 944.30 Sodium Hydro Sulphate 12.00 Organic Waste 7.70 MMA in Metha nol 10.00 Solvent Loss 40.00 Water 600.00 Total 1799.00 Total 1799.00

STAGE -7 INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage-6 100.00 Rabeprazole Sodium 100.00 Sodium hydroxide 13.00 IPA Rec. 280.00 Isopropyl Alcohol 300.00 Solvent Loss 15.00 Activated Carbon 10.00 Generated Water 5.00 Spent Carbon 10.00 Organic Residue 13.00 Total 423.00 Total 423.00

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50. Pranlukast

Process Description: Stage-1: To a stirred solution of Dimethyl Formamide and Methylene dichloride is added 4-(4- phenylbutoxy)benzoic acid. Charge drop wise thionyl chloride. After completion, distil out Methylene Dichloride under vacuum. Charge this reaction mass to stirred solution of 3- amino 2-hydroxy acetophenone in Methylene dichloride and pyridine at 0-5°C. After completion of reaction, charge Hydrochloric acid and separate layers. Wash with Sodium bicarbonate solution and evaporate organic layer to yield N-(2-hydroxy-3- (3-oxo-3-(1 H- tetrazol-5-yl) propanoyl)phenyl)- 4 - (4-phenylbutoxy) benzamide. Stage-2: N-(2-hydroxy- 3- (3-oxo- 3-(1 H-tetrazol-5-yl) propanoyl) phenyl)-4-(4-phenylbutoxy) benzamide and sulfuric acid were charged in reactor. Reaction mass was heated at 80° C for 2-3 hours. After completion, reaction mass was quenched in ice water to yield crude product. Stage-3: Pranlukast (crude) and ethyl acetate were charged in reactor and refluxed for 1 hour. Upon cooling at 10°C. Solid slurry was filtered to obtain pure product.

Route of Synthesis:

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Mass Balance:

Stage-1 Input QTY. (kgs) Output QTY. (kgs) 4-(4-phenylbutoxy)benzoic acid 100.00 Stage -1 125.00 1-(3-amino-2-hydroxyphenyl) 57.60 Methylene Dichloride(Reco) 570.00 Ethanone Methylene Dichloride(F/R) 588.00 Solvent Loss 18.00 Dimethyl Formamide 5.00 Effluent 769.30 Thionyl Chloride 59.00 Organic Residue 27.10 Pyridine 89.60 Process Emissions(SO2) 19.80 Hydrochloric acid 300.00 Sodium Bicarbonate 30.00 Water 300.00 Total 1529.20 Total 1529.20

Stage -2 Input QTY. (kgs) Output QTY. (kgs) Stage -1 125.00 Stage -2 106.30 Sulfuric Acid 500.00 Eff luent 1562.00 Water 1062.00 Organic Residue 18.8 Total 1687.00 Total 1687.00

Stage-3 Input QTY. (kgs) Output QTY. (kgs) Stage -2 106.30 Stage -3 106.30 Ethyl Acetate (F/R) 900.00 Ethyl Acetate 862.50 Effluent 15.00 Organic Residue 6.3 Total 1006.30 Total 1006.30

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51. Zonisamide

Process Description: Stage-I: 4-Hydroxycoumarin was reacted with hydroxylamine HCl in presence of potassium acetate anhydrous in methanol at desired temperature and appropriate condition. Methanol distillation, basification, dichloromethane washing and later acidification afforded Zonisamide Stage-I. Stage-II: Obtained solid was reacted with complex of chlorosulphonic acid and 1, 4-dioxane in ethylene dichloride. Quenching and later water removal and later chlorination using phosphorus oxychloride in toluene and animation using ammonia afforded Zonisamide Stage-II. Stage-III: Purification of Zonisamide Stage-II using acetone, water and activated charcoal afforded pure Zonisamide.

Route of Synthesis:

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Mass Balance:

STAGE-I INPUT QTY.(KGS) OUTPUT QTY.(KGS) Methanol 153.00 Stage -1 214.00 4Hydroxy Coumarin 195.30 Methanol Reco 137.7 Hydroxylamine hydrochloride 293.00 Methanol loss 15.3 Potassium acetate 413.00 Effluent 1338.30 Sodium hydroxide 20.00 Dry loss 30.00 Methylene Dichloride 490.00 Organic Residue 29.00 Hydrochloric Acid 100.00 Water 600.00 Total 17 64.30 Total 17 64.30

STAGE-2 INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage-1 214.00 Stage-2 171.00 Ethylene Dichloride 856.00 HCL gas 20.00 1,4 Dioxane 97.00 EDC Reco 770.4 CSA 120.00 Ammonia gas 130.00 Sodium Sulphate 78.00 Toluene reco 270.00 Toluene 300.00 Aq Effluent 1603.40 Phosphorus Oxychloride 20.00 Solvent loss 115.60 Water 14 00.00 Dry loss 35.00 Ammonia Gas 130.00 Total 32 15.00 Tota l 32 15.00

Stage -3 Input QTY.(kgs) Output QTY.(kgs) Zonisamide (Crude) 180.00 zonisamide 125.00 Ethyl Acetate 1445 Ml CF 1454.00 Activated Carbon 7.00 Carbon + Hyflow 25.00 Hyflowsupercell 7.00 Dry In Loss 35.00 Total 1639.00 Total 1639.00

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52. Telmisartan

Process description: Bibenzimidazole&bromomethyl ester is condensed in presence of sodium methoxide in DMF to give Telmi-I (Methyl–[[4-Methyl-4’6(1-methyl-1H benzimidazol-2-yl)-2-propyl- 1Hbenzimidazole -1yl] methyl] biphenyl-2-carboxylate).Telmi-I is hydrolyzed using potassium hydroxide in methanol & water mixture to give Telmisartan.

Route of Synthesis:

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Material Balance:

Stage-I Input QTY.(kgs) Output QTY.(kgs) Bibenzimidazole 186.7 (Stage - I) - termi -I 261.4 Bromo methyl ester 187.3 Dim ethyl formamide Rec 921.1 Sodium hydroxide 33.1 Acetone Rec 280.3 Dimethyl formamide 969.6 Methanol Rec 18.6 Acetone 295.1 Wastewater Water 1240.9 Water 1240.9 Sodium bromide 63 Organic waste Dimethyl formamide 9.7 Acetone 3 Methanol 0.2 Organics 63.1 Process Loss 51.4 Total 1692.7 Total 1692.7

Stage-II Input QTY.(kgs) Output QTY.(kgs) (Stage - I) - Termi -I 261.4 Telmisartan 222.2 Potassium hydroxide 76.1 Methanol Rec 3141.6 Acetic acid 470.6 Water 2660.1 Methanol 3304.6 Potassium acetate 133 Activated carbon 13.1 Spent carbon 21.9 Celite 8.8 Methanol 46.3 Water 2817 Water 170.8 Organics 33.8 Acetic acid 389.1 Process loss 132.8 Total 3810 Total 3810

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53. Rosuvastatin Calcium

Process Description: Stage-1: 4-Fluoro-Benzadehyde reacts with 4-Methyl-3-oxo-pentanoic acid ethyl ester in presence of Base to give Stage-1 as product. Stage-2: Stage-1product reacts with S-Methyl isothio urea and 2,3 Dichloro-5,6-dicyano benzo quinine in presence of HMPA to give stage-2as product. Stage-3: Stage-2 product reacts with meta-chloro peroxy benzoic acid to give Stage-4 as product and Meta chlorob enzoic acid as by-product. Stage-4 Stage-3 product reacts with methyl amine in presence of Ethanol solvent media to give Stage-4 as product. Stage-5 Stage-4 product reacts with Methane sulfonyl chloride in presence of Sodium hydride as catalyst to give Stage-5 as product. Stage-6 Stage-5product under goes reduction and oxidation in presence of Hydrogen gas to give Stage-6 as product. Stage-7 Stage-6 product reacts with methyl (3R)-3-(tert-butyldimethyl silyloxy)-5-oxo-6- triphenyl phosphoranyli denehexanoate. Stage-8 Stage-7 product reacts with Hydrogen fluoride in presence of Aceto nitrile as solvent media to give Stage-8 as product. Stage-9 Stage-8 product reacts with Sodium Boro hydride under goes hydrogenation to give Stage-9 as product. Stage-10 Stage-9 product reacts with Calcium chloride under goes saponification to give Rosuvastatin Calcium as product.

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Route of Synthesis:

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Mass Balance:

STAGE -1 INPUT QTY.(KGS) OUTPUT QTY.(KGS) 4-Fl uo roben zaldeh yde 52 .00 Stage-1 100 .00 4-Methyl-3-oxo-pentanoic 66.30 Methanol Recovery 237.00 acid ethyl ester Potassium hydroxide 23.50 Methanol Loss 12.00 Methyl I od ide 60 .00 Effluent water 590 .56 Methanol 250.00 Organic Residue 11.24 Water 500 .00 Total 951 .80 Total 951 .80

STAGE -2 INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage-1 100 .00 Stage-2 115 .00 S-Methyl isot hio ure a 35 .00 MDC R ecovery 474 .00 2,3-Dichloro-5,6- 85.00 MDC Loss 25.00 dicyano benzoquinone HMPA 100 .00 HMPA Recovery 94 .50 MDC 500 .00 HMPA Lo ss 5.00 Water 300 .00 Effluent water 307 .81 By-Produ ct 85 .75 Org an ic Resi due 12 .44 Total 11 20.00 Total 11 20.00

STAGE -3 INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage-2 115 .00 Stage-3 120 .00 Metachloroperoxybenzoicacid 118.68 MDC Recovery 284.50 MDC 300.00 MDC Loss 15.00 Water 500 .00 Effluent water 500 .50 Metachloro benzoic 107.67 acid Reu se Org an ic Resi due 6.01 Total 1033.68 Total 1033.68

STAGE-4 INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage-3 120 .00 Stage-4 96 .00 Methyl amine 10.20 Ethanol Recovery 238.00 Ethanol 250 .00 Ethano l Loss 12 .00 Metha nol 300 .00 Metha nol R ecovery 284 .50 Water 300.00 Methanol Loss 15.00 Effluent water 327.23 Org an ic Resi due 7.47

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Total 980 .20 Total 980 .20

STAGE-5 INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage-4 96.00 Stage-5 112.00 Methanesulfonyl chloride 35.00 Di methoxyethane Recovery 285.00 Sod ium hydride(60 %) 1.00 Di methoxyethan e Lo ss 15 .00 Di methoxyethane 300.00 Hydrochloric acid reuse 11.15 Org an ic Resi due 8.85 Total 432 .00 Total 432 .00

STAGE -6 INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage-5 112.00 Stage-6 95.00 Hydrogen 0.56 Toluene Recovery 284.00 DIBAL-H 1.00 Toluene Loss 15.00 Toluene 300.00 Ethanol Recovery 13.04 Org an ic Resi due 6.52 Total 413.56 Total 413.56

STAGE -7 INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage-6 95 .00 Stage-7 155 .00 Methyl(3R)-3-(tert butyl di methyl 144.55 N,N-Dimethyl formamide 280.00 silyloxy)-5-oxo-6- Recovery triphenylphosphoranylidenehexa noate Triethylamine 15 .00 N,N -Di methyl formamideLoss 15 .00 N,N-Dimethyl formamide 300.00 Effluent water 320.00 Water 300.00 Organic Residue 9.33 By-Produ ct 75 .22 Total 854.55 Total 854.55

STAGE-8 INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage-7 155 .00 Stage-8 120 .00 Hydrogenfluo ride 5.10 THF R ecovery 237 .00 THF 250.00 THF Loss 12.00 Ethyl acetate 300 .00 Ethyl acetate Recovery 285 .00 Ethyl acetate Loss 15.00 By-Product 34.24 Org an ic Resi due 6.86 Total 710.10 Total 710.10

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STAGE -9 INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage-8 120.00 Stage-9 115.00 Hydrogen 0.48 Ethyl acetate Recovery 237 .50 Diethyl methoxyborane 20.00 Ethyl acetate Loss 12.00 Sod ium bo rohydride 1.00 THF R ecovery 474 .50 Ethyl acetate 250 .00 THF Loss 25 .00 THF 500.00 Sodium Borohydride Residue 1.00 Org an ic Resi due 26 .48 Total 891 .48 Total 891 .48

STAGE -10 INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage-9 115.00 Rosuvastatin Calcium 100.00 Calci umc hloride 13 .00 Toluene Recovery 473 .50 Toluene 500.00 Toluene Loss 25.00 Ethyl acetate 500 .00 Ethyl acetate Recovery 475 .00 Water 250 .00 Ethyl acetate Loss 25 .00 Effluent water 262.82 Org an ic Resi due 16 .68 Total 13 78.00 Total 13 78.00

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54. Posaconazole

Process Description:

Stage-I: 4-Hydroxyphenyl-piperazinyl triazolone is added to Sodium hydroxide solution mixture. Then add (5R,Cis)-toluene-4-sulfonic acid-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1- yl)methyl tetrahydrofuran-3-yl methylester and Ethyl acetate, combine layers and wash with Sodium chloride solution. Then centrifuge the mass to collect the Stage-I material. Stage-II: Add Stage-I material, Add Pd/C then add Hydrochloric acid to the reaction mass. Hydrogenate the reaction mass adjust pH using Sodium Hydroxide. The wet material charge again into the reactor and add Acetone. Then centrifuge the mass to collect Stage-II (Posaconazole (crude)) material. Stage-III: Methylene Dichloride and Isopropyl Alcohol is used as a solvent. Filter the mass to remove the particles. Add Isopropyl Alcohol to the mass and heat the mass. Then cool the reaction mass and centrifuge the mass to collect the Posaconazole (Pure).

Route of Synthesis:

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Mass Balance:

Stage-I INPUT QTY.(KGS) OUTPUT QTY.(KGS) 4-Hydroxyphenyl -piperazinyl triazolone 14 Stage - I 18 (5R,Cis)-toluene-4-sulfonic acid-5-(2,4- 14 Recovery Ethyl Acetate 130.5 difluorophenyl)-5-(1H-1,2,4-triazol-1- Recovery Dimethyl 103.5 yl)methyl tetrahydrofuran-3-yl Sulfoxide methylester Recovery Isopropyl Alcohol 454.5 Loss of Ethyl Acetate 9.5 Sodium Hydroxide 2 Loss o f Dimethyl Sulfoxide 6.5 Hydrochloric Acid (35%) 2 Loss of Isopropyl Alcohol 25.5 Sodium Chloride 14 Effluent 320.19 Ethyl Acetate 140 Residue 7.81 Dimethyl Sulfoxide 110 Isopropyl Alcohol 480 Purified Water 300 Total 1076 Total 1076

Stage-II INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage -I 18 Stage – II 11 Hydrogen 0.5 Recovery Methanol 216 Hydrochloric Acid (35%) 6 Recovery Acetone 117 Sodium Hydroxide 7 Recovery Isopropyl Alcohol 150.5 Methanol 230 Loss of Methanol 14 Acetone 190 Loss of Ac etone 73 Isopropyl Alcohol 160 Loss of Isopropyl Alcohol 9.5 Palladium Carbon 9 Effluent 731 Purified Water 720 Residue 9.05 Palladium Carbon 9 Process Emission 0.45 Total 1340.5 Total 1340.5

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55. Ursodiol

Process Description: Stage-1: Preparation of Ketolithocholic acid. KSM (Chenodeoxycholic acid) oxidized using N-Bromosuccinamide in Acetone Water as solvent atroom temperature to get 7-Ketolithocholic acid crude which is further purified in Ethyl acetate,methanol, and water to get pure 7-Ketolithocholic acid (Stage-1).

Stage-2: Preparation of Ursodiol Crude 7-Ketolithocholic acid (Stage-1) reduced in presence of Metal Alloy (Ra/ni) in presence of BasePotassiumtert. Butoxide in IPA to get Ursodiolcrude.

Stage-3: Preparation of UrsodiolTriethyl amine Salt. Ursodiolcrude, which is salting with Triethyl amine in Acetone, water to get URSO TEA salt. This TEA salt is desalting with 10% HCl solution to get Ursodiol.

Route of Synthesis:

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Mass Balance:

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ANNEXURE - IV ______DETAILS OF WATER CONSUMPTION AND WASTEWATER GENERATION

WATER CONSUMPTION & WASTEWATER GENERATION:

Sr. Usage Proposed Scenario (KL/Day)

No. Water Wastewater

Consumption Generation

(KL/Day) (KL/Day) 1. Industrial Process 7.0 4.33 Boiler 1.5 0.2

Cooling 1.4 0.2

Washing 0.6 0.6 Total (Industrial) 10.5 5.33 2. Gardening 1.0 NIL 3. Domestic 1.5 1.2 Total 13.0 6.53

• Domestic wastewater (1.2 KL/day) will be treated and disposed in septic tank & soak pit.

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Water Balance Diagram:

Water: 13.0 KL/Day

(Fresh Water - 9.25 KL/Day + Reused - 3.75 KL/Day)

Domestic: Industrial: Gardening: 1.5 KL/Day 10.5 KL/Day 1.0 KL/Day

Septic Tank / Soak pit: 1.2 KL/Day

Process: Boiler: Cooling: Washing: 7.0 KL/Day 1.5 KL/Day 1.4 KL/Day 0.6 KL/Day

Process: Boiler: Cooling: Washing:

4.33 KL/Day 0.2 KL/Day 0.2 KL/Day 0.6 KL/Day

5.33 KL/Day in ETP for Neutralization

0.33 MT/Day --> TSDF 5.33 KL/Day --> MEE

3.75 KL/Day MEE Condensate will be reused for Boiler, Cooling, Washing and gardening

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ANNEXURE - V ______DETAILS OF EFFLUENT TREATMENT PLANT (ETP)

PROCESS DESCRIPTION OF EFFLUENT TREATMENT PLANT: First all non-toxic and biodegradable streams of wastewater shall be collected in Equalization cum Neutralization Tank (ENT-01) where the continuous addition and stirring of Lime solution is done to maintain neutral pH of wastewater from Lime Dosing Tank (LDT-01) as per requirement by gravity. Pipe grid is provided at bottom of the ENT-01 to keep all suspended solids in suspension and to provide proper mixing by air supplied through air blowers (B-01).

Then after, neutralized wastewater shall be pumped to Flash Mixer (FM-01). Alum and Polyelectrolyte shall be dosed from Alum Dosing Tank (ADT-01) and Polyelectrolyte Dosing Tank (PEDT-1) respectively by gravity into FM-01 to carry out coagulation by using a Flash Mixer. Then after, coagulated wastewater shall be settled in Primary Settling tank (PST-01). Clear supernatant from PST-01 shall be collected in Intermediate Sump (IS-01). Neutralized wastewater shall be evaporated in MEE and MEE Condensate will be reused for cooling tower, boiler, washing and gardening purpose.

Sludge settled in PST-01 and MEE Sludge shall be sent to Sludge Drying Beds (SDBs-A/B) where, dewatering shall be carried out before storage in HWSA and ultimate disposal to TSDF.

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SIZE OF TANKS

S.N. Name of unit Size (m x m x m) No. MOC/ Remark Flow = 5 KLD Equalization cum Neutralization 1 1.6 x 1.6 x 2.0 1 RCC M25 Tank (ENT-01) 2 Flash Mixer (FM-01) 0.8x 0.8 x 1.5 LD 1 MSFRP 3 Primary Settling Tank(PST-01) 1.5 x 1.0 x 1.2 1 MSFRP 4 Intermediate Sump (IS-01) 1.5 x 1.0 x 1.2 1 MSFRP 5 Dual Media Filter (DMF-01) 300 lit/hr 1 FRP 6 Treated Effluent Sump (TES-01) 2.5 x 2.0 x 2.0 1 RCC M25 7 Lime Dosing Tank (LDT-01) 250 lit 1 HDPE 8 Alum Dosing Tank (ADT-01) 250 lit 1 HDPE 9 Poly Dosing Tank (PDT-01) 100 lit 1 HDPE Bk. Mas. With 10 Sludge Drying Beds (SDBs-A/B) 2.0 x 3.0 2 PCC Bedding+ filling Media

RCC M25 = REINFORCED CEMENT CONCRETE (M 25 GRADE) PCC = PLAIN CEMENT CONCRETE HDPE = HIGH DENSITY POLY ETHELINE BK.MAS. = BRICK MASONARY

EXPECTED CHARACTERISTICS OF WASTEWATER BEFORE & AFTER TREATMENT

Sr. Parameter Characteristics (mg/L) CETP Inlet Norms No. Untreated Treated (mg/L) 1. pH 3-9 6.5-8.5 6.5-8.5 2. SS 150 70 100 3. COD 3000 2500 3000

4. BOD 3 1000 800 1200

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Details of MEE:

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Flow Diagram of Effluent Treatment Plant:

MEE Cond. - MEE Reused

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ANNEXURE - VI ______DETAILS OF AIR POLLUTION CONTROL SYSTEM

Flue Gas Emission: The flue gas emission through stack attached to IBR Boiler, Thermo pack & DG Set shall conform to the following standards: Sr. Process stack Height from Consumption Air pollution Expected No. attached to ground level of fuel control system Pollutants 1 IBR boiler 11 meter Natural Gas = Adequate Stack PM = 150 mg/Nm 3 3 (2 TPH) 300 SM /Day height will be SO 2 = 100 ppm

provided. NO x = 50 ppm 2 Thermo pack 13 meter Natural Gas = Adequate Stack (2 Lakhs 200 SM 3/Day height will be Kcal/hr.) provided. 3 DG Set 11 meter Diesel = Adequate Stack (100 KVA) 50 Liter/Day height will be provided.

Process Gas Emission: The details of process gas emission from reaction vessel are as below: Sr. Process stack Height from Consumption Air pollution Expected No. attached to ground level of fuel control system Pollutants 3 1 Reaction 11 meter -- Two Stage Cl 2 = 9 mg/Nm Vessel Scrubber HCl = 20 mg/Nm 3

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ANNEXURE - VII ______DETAILS OF HAZARDOUS WASTE GENERATION, STORAGE & DISPOSAL

Sr. Type of waste Category Quantity Disposal Method No. 1 ETP Sludge 35.1 5 Collection, Storage, Transportation MT/Month & Disposal to TSDF site (M/s. BEIL or M/s. PSWML) 2 Discarded Bags/ 33.1 800 Collection, Storage, Transportation, Drums/ Carboys Nos./Month Decontamination and sell to GPCB authorized vendors 3 Process Residue -- 5 Collection, Storage, Transportation MT/Month & sent to cement industries for co- processing or sent to CHWIF for incineration. 4 Used oil 5.1 0.075 Collection, Storage, transportation KL/Month and disposal by sell to registered reprocessor 5 MEE Salt -- 10 Collection, Storage, Transportation MT/Month & Disposal to TSDF site (M/s. BEIL or M/s. PSWML)

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ANNEXURE - VIII ______DETAILS OF HAZARDOUS CHEMICALS STORAGE & HANDLING

Sr. Name of the Type of Kind of Max. Qty. Storage condition No. Material Hazard storage to be stored i.e. Temp., Pressure (MT) 1 Acetic Acid Corrosive Drums 4745.50 Keep container in a cool, well- ventilated area. Keep container tightly closed 2 Acetic Anhydride Flammable Drums 471.00 Keep container in a cool, well- ventilated area. Keep container tightly closed 3 Acetone Corrosive Drums 115385.50 Keep container in a cool, well- ventilated area. Keep container tightly closed 4 Activated carbon Flammable Store in 365.55 Keep container in a cool, well- Bag/ ventilated area. Keep container Drums tightly closed 5 Aluminium Corrosive Store in 2136.00 Keep container tightly closed. Chloride Bag/ Keep container in a cool, well- Drums ventilated area. 6 Ammonia Gas Corrosive Cylinder 520.00 Store in a cool and well ventilated place 7 Ammonia Corrosive Drums 1680.00 Store in a cool and well Solution ventilated place 8 Sodium Sulphate Corrosive Store in 412.50 Keep container tightly closed. Bag/ Keep container in a cool, well- Drums ventilated area. Hygroscopic 9 Aniline Toxic Drums 170.00 Store in light-resistance container. Keep container in a cool, well-ventilated area. Keep container tightly closed 10 Benzene Sulfonic Corrosive Drums 320.00 Keep container tightly closed. Acid Keep container in a cool, well- ventilated area. 11 Bromine Corrosive Glass 1298.00 Keep container tightly closed. bottle Keep container in a cool, well- ventilated area. 12 Butanol Flammable Drums 515.00 Keep container in a cool, well- ventilated area. Keep container tightly closed 13 Chloro Acetyl Flammable Drums 710.00 Keep container tightly closed. Chloride Keep container in a cool, well- ventilated area

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14 Caustic lye Corrosive Store in 366.50 Keep container tightly closed. Bag/ Keep container in a cool, well- Drums ventilated area. Hygroscopic 15 Citric acid Corrosive Store in 30.00 Keep container tightly closed. Bag/ Keep container in a cool, well- Drums ventilated area 16 Hydrochloric Acid Corrosive Drums 17169.85 Keep container tightly closed. Keep container in a cool, well- ventilated area. 17 Di Methyl Flammable Drums 8935.00 Keep container in a cool, well- Formamide ventilated area. Keep container tightly closed 18 Pyridine Corrosive Drums 1792.00 Keep container in a cool, well- ventilated area. Keep container tightly closed 19 Formaldehyde Flammable Drums 351.40 Store away from sources of heat or ignition, strong alkalis, acids, combustibles and oxidizing agents. 20 Hydrogen gas Flammable Cylinder 78.50 Keep away from heat. Keep away from sources of ignition. Keep container tightly closed. Keep in a cool, well-ventilated place 21 Iso Propyl Flammable Drums 62347.00 Keep container in a cool, well- Alcohol ventilated area. Keep container tightly closed 22 Liq Ammonia Corrosive Cylinder 705.00 Store in a cool, well-ventilated place. Store and use with adequate ventilation. 23 Liq. Bromine Flammable Store in 1298.00 Keep container tightly closed. Bag/ Keep container in a cool, well- Drums ventilated area 24 Methanol Flammable Drums 31851.7 Keep away from heat. Keep away from sources of ignition. Keep container tightly closed. Keep in a cool, well-ventilated place 25 Nitric acid Corrosive Drums 75.00 Keep container in a cool, well- ventilated area. Separate from acids, alkalies, reducing agents and combustibles. 26 Sodium Nitrite Corrosive Store in 575.00 Keep container in a cool, well- Bag/ ventilated area. Separate from Drums acids, alkalies, reducing agents 27 Succinic Acid Corrosive Store in 133.00 Keep container tightly closed. Bag/ Keep in a cool, well-ventilated

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Drums place 28 Sulfuric acid Corrosive Drums 10270.00 Keep container tightly closed. Keep in a cool, well-ventilated place 29 Tartric Acid Corrosive Store in 148.00 Keep container tightly closed. Bag/ Keep container in a cool, well- Drums ventilated area. 30 Toluene Flammable Drums 53630.00 Keep away from heat, sparks, and flame. Keep away from sources of ignition. Keep container closed 31 Xylene Flammable Drums 240.00 Keep away from heat, sparks, and flame. Keep away from sources of ignition. Keep container closed 32 Iso Propyl Flammable Drums 8655.00 Keep away from heat. Keep Acetate away from sources of ignition. Keep container tightly closed. Keep in a cool, well-ventilated place

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ANNEXURE - IX ______SOCIO - ECONOMIC IMPACTS

1) Employment Opportunities The manpower requirement for the proposed expansion project is being expected to generate some permanent jobs and secondary jobs for the operation and maintenance of plant. This will increase direct / indirect employment opportunities and ancillary business development to some extent for the local population. This phase is expected to create a beneficial impact on the local socio-economic environment.

2) Industries Required raw materials and skilled and unskilled laborers will be utilized maximum from the local area. The increasing industrial activity will boost the commercial and economical status of the locality, to some extent.

3) Public Health The company regularly examines, inspects and tests its emission from sources to make sure that the emission is below the permissible limit. Hence, there will not be any significant change in the status of sanitation and the community health of the area, as sufficient measures have been taken and proposed under the EMP.

4) Transportation and Communication Since the existing factory is having proper linkage for the transport and communication, the development of this project will not cause any additional impact. In brief, as a result of the proposed there will be no adverse impact on sanitation, communication and community health, as sufficient measures have been proposed to be taken under the EMP. The proposed scenario is not expected to make any significant change in the existing status of the socio - economic environment of this region.

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ANNEXURE - X ______PROPOSED TERMS OF REFERENCE FOR EIA STUDIES

1. Project Description • Justification of project. • Promoters and their back ground • Project site location along with site map of 5 km area and site details providing various industries, surface water bodies, forests etc. • Project cost • Project location and Plant layout. • Existing infrastructure facilities • Water source and utilization including proposed water balance. • List of Products & their capacity • Details of manufacturing process of proposed products • List of hazardous chemicals • Mass balance of each product • Storage and Transportation of raw materials and products.

2. Description of the Environment and Baseline Data Collection • Micrometeorological data for wind speed, direction, temperature, humidity and rainfall in 10 km area. • Existing environmental status Vis a Vis air, water, noise, soil in 10 km area from the project site. • Ground water quality at 8 locations within 10 km. • Complete water balance

3. Socio Economic Data • Existing socio-economic status, land use pattern and infrastructure facilities available in the study area were surveyed.

4. Impacts Identification And Mitigatory Measures • Identification of impacting activities from the proposed project during construction and operational phase. • Impact on air and mitigation measures including green belt • Impact on water environment and mitigation measures • Soil pollution source and mitigation measures • Noise generation and control. • Solid waste quantification and disposal. • Control of fugitive emissions

5. Environmental Management Plan • Details of pollution control measures • Environment management team • Proposed schedule for environmental monitoring including post project

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6. Risk Assessment • Objectives, Philosophy and methodology of risk assessment • Details on storage facilities • Process safety, transportation, fire fighting systems, safety features and emergency capabilities to be adopted. • Identification of hazards • Consequence analysis • Recommendations on the basis of risk assessment done • Disaster Management Plan.

7. Information for Control of Fugitive Emissions 8. Information on Rain Water Harvesting 9. Green Belt Development plan

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ANNEXURE - XI ______COPY OF PLOT ALLOTMENT LETTER

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ANNEXURE - XII ______COPY OF GIDC WATER SUPPLY CERTIFICATE

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ANNEXURE - XIII ______MEMBERSHIP CERTIFICATE OF CETP (M/s. PETL)

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ANNEXURE - XIV ______MEMBERSHIP CERTIFICATE OF COMMON HAZARDOUS WASTE DISPOSAL FACILITY & COMMON INCINERATION FACILITY (M/s. BEIL)

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ANNEXURE - XV ______TOPOSHEET

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