(See Paragraph – 6) FORM 1 (I) Basic Information S. No. Item Details 1 Name of the Project/S M/S. Teck Bond Labo

APPENDIX I (See paragraph – 6)

FORM 1

(I) Basic Information

S. Item Details No. 1 Name of the Project/s M/s. Teck Bond Laboratories Pvt. Ltd., (APIs & API Intermediate Manufacturing Unit) Application for EC Validity extension 2 S.No. in the Schedule 5 (f) 3 Proposed capacity / area / length / Production capacity : 240 TPA tonnage to be handled / command area / (Four products will be manufacture at a time lease area / number of wells to be drilled on campaign basis out of 18 products) 4 New/ Expansion / Modernization Application for EC Validity extension 5 Existing Capacity / Area etc., Application for EC Validity extension Area : 2.72 hectares 6 Category of Project ie., ‘A’ or ‘B’ Category ‘A’ 7 Does it attract the general Condition? If No Yes, Please specify 8 Does it attract the specific condition? If No Yes, Please specify 9 Location Plot/Survey/Khasra No. Sy. No. 168,170/A, 170/AA, 173/1, 173/1A. Village Anantharam Tehsil Jinnaram District Medak State Telangana 10. Nearest railway station / Dabilpur Railway Station – 10 km (SE) airport along with distance in km. Shamshabad (Hyderabad) – 51 km (S) (aerial distance) 11. Nearest Town, City, Jinnaram – 9 km (SW) District Headquarters along with distance Hyderabad ORR – 12km (S) in kms. Sangareddy – 32 km (SSW) District Headquarters – Medak – 39 km (NNW) (aerial distance) 12. Village Panchayats, Zilla Parishad, Village Panchayat address (local body): Municipal Corporation, Local body Gram Panchayat Office, (complete postal addresses with Anantaram Village, telephone nos. to be given) Jinnaram Mandal, Medak District, Telangana State 13 Name of the applicant M/s. Teck Bond Laboratories Pvt. Ltd., Mr. T. Bose Babu Managing Director 14 Registered Address M/s. Teck Bond Laboratories Pvt. Ltd., 96/C, LIGH, Vengala Rao Nagar, Hyderabad, Telangana – 500 038. 15. Address for correspondence: Name Mr. T. Bose Babu

Designation(Owner/Partner/ CEO) Managing Director Address M/s. Teck Bond Laboratories Pvt. Ltd., 96/C, LIGH, Vengala Rao Nagar, Hyderabad, Telangana – 500 038. Pin Code 500038 E-mail [email protected] Telephone No. 040-23811864 Fax No. - 13 Details of Alternative Sites examined, if Not Applicable. any, Location of these sites should be Application for EC Validity extension. shown on a top sheet. 14 Interlined projects Nil 15 Whether separate application of interlined Not Applicable project has been submitted 16 If yes, date of submission Not Applicable 17 If no, reason Not Applicable 18 Whether the proposal involves Not applicable approval/clearance under: (a) The Forest (Conservation)Act, 1980 (b) The Wildlife (Protection) Act, 1972 (c) The C.R.Z Notification, Act, 1991 19 Forest land involved (hectares) Nil 20 Whether there is any litigation pending Nil 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.,)

(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.)

S. Information/Checklist confirmation Yes/No Details thereof (with approximate No. quantities /rates, wherever possible) with source of information data 1.1 Permanent or temporary change in Yes Application for EC Validity extension land use, land cover or topography Area of the project is 2.72 Hectares. including increase in intensity of land Plant layout is enclosed as Annexure – use (with respect to local land use I. plan) 1.2 Clearance of existing land, vegetation No Not envisaged. and buildings?

1.3 Creation of new land uses? No As per the Plant layout enclosed as Annexure-I. 1.4 Pre-construction investigations e.g. Yes Application for EC Validity Extension. bore houses, soil testing? 1.5 Construction works? Yes As per the Plant layout enclosed as Annexure-I. 1.6 Demolition works? No Not envisaged. 1.7 Temporary sites used for construction No Construction workers are coming from works or housing of construction the nearby villages. No accommodation workers? for the construction workers. 1.8 Above ground buildings, structures or Yes As per the Plant layout enclosed as earthworks including linear structures, Annexure-I. cut and fill or excavations 1.9 Underground works including mining No Not envisaged or tunneling? 1.10 Reclamation works? No Not envisaged 1.11 Dredging? No Not envisaged 1.12 Offshore structures? No Not envisaged 1.13 Production and manufacturing Yes Manufacturing process of the EC/CFE processes? permitted APIs is enclosed as Annexure-II. 1.14 Facilities for storage of goods or Yes Store room for all goods except for bulk materials? solvents & high quantity liquid raw materials, which will be stored in above ground tanks. 1.15 Facilities for treatment or disposal of Yes Schematic flow sheet for treatment and solid waste or liquid effluents? disposal of solid waste & liquid effluents is presented and enclosed as Annexure-III. 1.16 Facilities for long term housing of No Not envisaged. operational workers? 1.17 New road, rail or sea traffic during No Not envisaged. construction or operation? 1.18 New road, rail, air waterborne or other No Not envisaged. transport infrastructure including new or altered routes and stations, ports, airports etc? 1.19 Closure or diversion of existing No Not envisaged. transport routes or infrastructure leading to changes in traffic movements? 1.20 New or diverted transmission lines or No Not envisaged. pipelines? 1.21 Impoundment, damming, culverting, No Not envisaged. realignment or other changes to the hydrology of watercourses or aquifers? 1.22 Stream crossings? No Not envisaged. 1.23 Abstraction or transfers of water form No Water requirement is met from the ground or surface waters? Tankers / bore well (Ground water) 1.24 Changes in water bodies or the land No Not envisaged. surface affecting drainage or run-off?

1.25 Transport of personnel or materials Yes The construction material will be for construction, operation or obtained locally and will be transported decommissioning? through roads. The sources of raw materials and machinery for operation will vary based on market driven forces, which will be transported via roads. 1.26 Long-term dismantling or No Not envisaged. decommissioning or restoration works? 1.27 Ongoing activity during No Not envisaged. decommissioning which could have an impact on the environment? 1.28 Influx of people to an area in either Yes Workers / employees will be increased temporarily or permanently? and the working hours are in shifts / general. 1.29 Introduction of alien species? No Not envisaged. 1.30 Loss of native species or genetic No Not envisaged. diversity? 1.31 Any other actions? No -

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): S. Information/checklist confirmation Yes/No Details thereof (with approximate No. quantities /rates, wherever possible) with source of information data

2.1 Land especially undeveloped or No Application for EC Validity extension agricultural land (ha) 2.2 Water (expected source & competing Yes Water will be sourced from Ground users) unit: KLD water. Water Balance is enclosed as Annexure-IV. 2.3 Minerals (MT) No Not applicable 2.4 Construction material – stone, Yes Construction materials are procured from aggregates, sand / soil (expected the local market and construction is source – MT) based on the plant layout enclosed as Annexure – I. 2.5 Forests and timber (source – MT) No Not applicable 2.6 Energy including electricity and fuels Yes 1200 KVA power (electricity) will be (source, competing users) Unit: fuel required for the existing and proposed (MT), energy (MW) project. Coal : 40.0 TPD for 10.0 TPH and standby 3.0 & 1.0 TPH. Diesel: 175 liters/hr for 165 & 200 KVA, 500 KVA D.G. set (standby power). 2.7 Any other natural resources (use No - 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.

S.No. Information/Checklist confirmation Yes/No Details thereof (with approximate quantities/rates, wherever possible) with source of information data 3.1 Use of substances or materials, which Yes List of hazardous chemicals used in are hazardous (as per MSIHC rules) the permitted products are enclosed in to human health or the environment Annexure-V. (flora, fauna, and water supplies) 3.2 Changes in occurrence of disease or No Effluent will be segregate and treated affect disease vectors (e.g. insect or for reuse within the plant premises water borne diseases) (zero discharge). All solid waste will be stored in the covered platform with Leachate collection system and sent to TSDF. Process emissions will be scrubbed in the scrubbers. 3.3 Affect the welfare of people e.g. by Yes This is an existing permitted industry. changing living conditions? The welfare of the people will have positive effects as the new proposed expansion project will give the additional employment to the locals and industry will continue in participating in the village welfare measures. Developing the greenbelt in and around the plant site and along the village’s roads. 3.4 Vulnerable groups of people who No Plant site is more than 1.5 km away could be affected by the project e.g. from the nearest habitation. hospital patients, children, the elderly etc., 3.5 Any other causes No -

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

S.No. Information/Checklist confirmation Yes/No Details thereof (with Approximate quantities/rates, wherever possible) with source of information data 4.1 Spoil, overburden or mine wastes No Not envisaged. 4.2 Municipal waste (domestic and or No Commercial waste generated from the commercial wastes) administration building will be sold to scrap vendors. 4.3 Hazardous wastes (as per Hazardous Yes Hazardous wastes generated from the Waste Management Rules) products are presented in Annexure- VI. 4.4 Other industrial process wastes Yes Other industrial process wastes from the products manufacturing are given in Annexure-VI. 4.5 Surplus product No Production capacity will be ensured for approved quantity. Hence there will not be any surplus production envisaged. 4.6 Sewage sludge or other sludge from Yes ETP sludge is being sent to

effluent treatment TSDF/TSPCB Authorized vendors and continue the same 4.7 Construction or demolition wastes No Not envisaged 4.8 Redundant machinery or equipment No Not applicable 4.9 Contaminated soils or other materials No All precautionary measures will be ensured to avoid the soil contamination. 4.10 Agricultural wastes No Nil 4.11 Other solid wastes No Please refer Annexure-VI for details of other solid wastes from the permitted products

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

S.No. Information/Checklist confirmation Yes/No Details thereof (with Approximate quantities/rates, wherever possible) with source of information data 5.1 Emissions from combustion of fossil Yes Details of fuel used for Boiler, fuels from stationary or mobile sources D.G.Sets enclosed in Annexure-VII. 5.2 Emissions from production processes Yes Emission from process reactions from the permitted products are given in Annexure-VIII. 5.3 Emissions from materials handling Yes Pumps will be used for handling of including storage or transport liquid raw materials and trolleys will be used for Solid / Powder type raw materials. Vent condensers will be provided for all storage tanks. 5.4 Emissions from construction activities Yes Dust emissions during construction including plant and equipment activities will be suppressed by water sprinkling system. 5.5 Dust or odours from handling of Yes Dusting will be there due to materials including construction construction work and due to materials, sewage and waste transportation of goods and materials. It will be reduced by spraying of water. 5.6 Emissions from incineration of waste Yes Continue to send all Incinerable Hazardous waste to TSDF for incineration / Cement industries for used as alternate fuel. 5.7 Emissions from burning of waste in No All construction debris will be used open air (e.g. slash materials, as filling material for roads and other construction debris) waste materials are sold as scrap. 5.8 Emissions from any other sources No NIL

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

S.No. Information/Checklist Yes/No Details thereof (with confirmation Approximate quantities/rates, wherever possible) with source of information data with source of information data 6.1 From operation of equipment e.g. Yes Noise will be generated from the engines, ventilation plant, crushers utilities section. Silencers are provided for D.G. Sets and other utilities equipment and these will be provided in separate room. 6.2 From industrial or similar processes Yes Noise will be generated from the pumps, motors, centrifuges etc., which will be controlled by proper maintenance and procuring the sound proof equipments. 6.3 From construction or demolition Yes Noise will be generated during construction phase, which will be temporary and for short time. 6.4 From blasting or piling No Not envisaged. 6.5 From construction or operational Yes Noise will be generated from the traffic transportation vehicles. 6.6 From lighting or cooling systems No NIL 6.7 From any other sources No NIL

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:

S.No. Information/Checklist confirmation Yes/No Details thereof (with Approximate quantities/rates, wherever possible) with source of information data 7.1 From handling, storage, use or Yes Accidental spillages such as spillage of hazardous materials wastewater /solid wastes /raw materials are possible and the risk of this would be limited to within the premises of the manufacturing facility. Precautionary measures will be implemented for proposed industry for spillage control and to avoid contamination of land or water from the pollutants or raw materials. Suggestions from the safety consultants will be followed to avoid the risk and prevent accidents. 7.2 From discharge of sewage or other Yes Possibility of contamination of land or effluents to water or the land water is there due to the discharge of (expected mode and place of trade effluent to water or land. discharge) However, all the effluents are stored in 1 meter above ground level RCC

tanks.

All the tanks of the effluent treatment plant will be above ground level. In phase 2 expansion after full fledge treatment all the treated effluent will be reused within the premises. Domestic waste water sent to ETP and treated water used back in Cooling Towers / Boilers. 7.3 By deposition of pollutants emitted to Yes Possibility of deposition of pollutants air into the land or into water emitted to air into the land or into water cannot be ruled out and the precautions taken by the industry to control such emissions by adopting the suitable controlling equipment like cyclone separators, scrubbers etc., 7.4 From any other sources No NIL 7.5 Is there a risk of long term build up of No Not envisaged. 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

S.No. Information/Checklist confirmation Yes/No Details thereof (with Approximate quantities/rates, wherever possible) with source of information data 8.1 From explosions, spillages, fires etc Yes All safety precautions will be taken by from storage, the industry to avoid such accidents. handling, use or production of hazardous substances 8.2 From any other causes Yes Static Electricity 8.3 Could the project be affected by natural Yes Not envisaged. 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

S. Information/Checklist confirmation Yes/No Details thereof (with Approximate No. quantities/rates, wherever possible) with source of information data

9.1 Lead to development of supporting. lities, ancillary development or development stimulated by the project which could have

impact on the environment e.g.:

• Supporting infrastructure (roads, Yes Supporting infrastructure such as power supply, waste or waste water Roads, Power supply, waste or treatment, etc.) wastewater treatment etc., may have impacts on the project activities. However the impact from such activities will be limited as this is existing industry and supporting infrastructure required for the industry is under construction.

• housing development NO All employees will be coming from near by villages.

• extractive industries Yes Possibility of extractive industries cannot be ruled out.

• supply industries Yes Supply industries will be supplying various raw material required for the operation of the industry. • other No. 9.2 Lead to after-use of the site, which No Not envisaged. could have an impact on the environment 9.3 Set a precedent for later developments No Not envisaged. 9.4 Have cumulative effects due to Yes Existing Industry proximity to other existing or planned projects with similar effects

(III) Environmental Sensitivity S.No. Areas Name/ Aerial distance (within 15 km.) Identity Proposed project location boundary

1 Areas protected under international Yes Following Reserved forest blocks are conventions, present such as national or local legislation for their • Narsapur R.F (Dense Mixed Jungle) ecological, landscape, cultural or other >3.5 Km (W) related value • Nawabpet R.F (Fairly Dense Scrub) >2Km (N) • Kunkunta R.F (Dense Scrub) >4.4 Km (NE) • Parikabanda RF (Dense Mixed Jungle) >7 km (S) • Dabilpur RF (Dense scrub) > 8 km (SE) 2 Areas which are important or sensitive No There are no wetlands near the plant for ecological reasons - Wetlands, site. watercourses or other water bodies, coastal zone, biospheres, mountains, forests 3 Areas used by protected, important or No NIL sensitive Species of flora or fauna for

breeding, nesting, foraging, resting, over wintering, migration 4 Inland, coastal, marine or underground Yes No water bodies in less than 1.5 km. waters Gummadidala erra cheruvu – 1.8 km (SW) Erra Cheruvu – 2.5 km (NW) 5 State, National boundaries No NIL 6 Routes or facilities used by the public No Industry is about 2 Km from State for access to recreation or other tourist, Highway (Hyderabad to Medak) pilgrim areas 7 Defense installations No NIL 8 Densely populated or built-up area No Hyderabad (State capital) is at a distance of 40 km from the industry. 9 Areas occupied by sensitive man- No There is no habitation or sensitive made land uses man-made land used within 1.5 km (hospitals, schools, places of worship, distance. communityfacilities) 10 Areas containing important, high No Not Applicable quality or scarce resources (ground water resources, surface resources, forestry, agriculture, fisheries, tourism, minerals) 11 Areas already subjected to pollution or NO Not Applicable environmental damage. (those where existing legal environmental standards are exceeded) 12 Areas susceptible to natural hazard No The area is not known for these natural which could cause the project to hazards. Seismically, this area is present environmental problems categorized under Zone II as per IS- (earthquakes, subsidence, landslides, 1893 (Part-I)-2002. erosion, flooding or extreme or adverse climatic conditions)

(IV). Proposed Terms of Reference for EIA studies Application for EC validity Extension. EC copy is enclosed as Annexure-IX.

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 : 30-6-2016 Place : Hyderabad Signature of the applicant With Name and Full Address (Project Proponent / Authorized Signatory) 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 and the recommendations of the State Coastal Zone Management Authority. Simultaneous action shall also be taken to obtain the requisite clearance under the previous of the C.R.Z Notification, 1991 for the activities to be located in the C.R.Z. 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 vix-a-vix the project location and the recommendations or comments of the chief Wildlife Warden thereon.

List of Annexures

I. Plant layout II. Manufacturing process of the Proposed Products. III. Effluent treatment plant IV. Water balance V. List of Hazardous Chemicals used in the proposed products VI. Details of Hazardous solid waste and other waste. VII. Fuel consumption and Emissions details of Boiler and D.G. Sets VIII. Details of emissions from process reactions. IX. EC Copy

Other Annexures X. Topomap XI. CFE 2011 XII. CFO 2013

ANNEXURE - I

12 ANNEXURE - II

PRODUCT : Sparfloxacin

Description :

Stage-1 : Pentafluorobenzoyl Chloride on condensation with Diethyl Malonate in the presence of Magnesium Methoxide gives Diester derivative. Which on hydrolysis in the presence of Sulfuric Acid gives Beta Keto Ester Derivative.

Stage-2 : Beta Keto Ester on condensation with Triethyl orthoformate in the presence of Acetic acid gives Ethoxy compound which on condensation with Cyclopropylamine gives Amino compound which on cyclisation gives Q-Ester Compound.

Stage-3 : Q-Ester on condensation with Benzylamine in presence of Triethylamine gives Benzyl Compound.

Stage-4 : Benzyl Compound on reduction with Hydrogen on Palladium Carbon gives Amino Compound.

Stage-5 : Amino Compound undergoes hydrolysis in presence of Sulfuric Acid gives Q-Acid.

Stage-6 : Q-Acid on condensation with Dimethyl Piperazine in presence of Potassium Carbonate gives Sparfloxacin.

13 ANNEXURE - II

PRODUCT : Sparfloxacin

Flow Chart

Pentafluorobenzoyl Chloride Magnesium Methoxide Sol.Recovery Ethanol Evaporation Loss Diethyl Malonate Stage I Effluent Acetone Organic Residue Sulfuric acid Inorgainc Solid Waste Water Process Emissions

Stage-1 Triethyl Orthoformate Sol.Recovery Acetic Acid Evaporation Loss Cyclopropylamine Stage II Effluent Toluene Organic Residue Potassium Carbonate Process Emissions Water

Stage-2 Benzylamine Sol.Recovery Potassium Hydroxide Stage III Evaporation Loss Toluene Effluent Water Organic Residue

Stage-3 Sol.Recovery Carbon Evaporation Loss Methanol Effluent Stage IV Hydrogen Organic Residue Hyflo Spent Carbon Water Process Emissions

Stage-4 Sulfuric Acid Stage V Effluent Water

Stage-5 Dimethyl Piperazine Sol.Recovery Potassium Carbonate Evaporation Loss Stage VI Toluene Effluent Methanol Organic Residue Water Process Emissions

Sparfloxacin

14 ANNEXURE - II

PRODUCT : Mirtazapine

Description :

Stage-1 : 1-Methyl-3-phenyl piperazine is condensed with 2-Chloro nicotinonitrile in Dimethylformamide in presence of Sodium Hydroxide and Potassium Fluoride to obtain Mirtazapine Stage-I material.

Stage-2 : Hydrolysis of Mirtazapine Stage-I material with Sodium Hydroxide and Hydrochloric Acid in presence of Toluene, Methylene Dichloride and Ethanol solvent media gives the corresponding carboxylic acid (Mirtazapine Stage-II) material.

Stage-3 : Subsequent Mirtazapine Stage-II material reduction with Lithium Aluminum Hydride in refluxing Tetrahydrofuran and Diisopropyl Ether provides Mirtazapine Stage-III material.

Stage-4 : Mirtazapine Stage-III material is cyclized in presence of Concentrated Sulfuric Acid in Methylene Dichloride and Diisopropyl Ehter media to produce Mirtazapine which is finally purified in Cyclohexane to give pure Mirtazapine.

15 ANNEXURE - II

PRODUCT : Mirtazapine

Flow Chart

1-Methyl-3-phenyl piperazine 2-Chloro nicotinonitrile Dimethylformamide Sol.Recovery Ethyl Acetate Evaporation Loss Stage I Potassium Fluoride Effluent Sodium Hydroxide Organic Residue Sodium Chloride Inorgainc Solid Waste Water

Stage-1 Toluene Sol.Recovery Methylene Dichloride Evaporation Loss Ethanol Stage II Effluent Sodium Hydroxide Organic Residue Hydrochloric Acid (35%) Process Emissions Water

Stage-2 Tetrahydrofuran Sol.Recovery Diisopropyl Ether Evaporation Loss Stage III Lithium Aluminum Hydride Effluent Sodium Hydroxide Organic Residue Water Process Emissions

Stage-3 Methylene Dichloride Sol.Recovery Diisopropyl Ether Evaporation Loss Cyclohexane Effluent Stage IV Sulfuric Acid Organic Residue Sodium Hydroxide Inorgainc Solid Waste Carbon Spent Carbon Water

Mirtazapine

16 ANNEXURE - II

PRODUCT : Topiramate

Description :

Stage-1 : D-Fructose reacts with Acetone and Sulfuric acid at 0-5oC for 10 hrs. After reaction complies adjust the PH with Sodium Hydroxide and separate the inorganic salts. Distill out organic layer, isolate the material in Isopropyl Alcohol and Hexane at 10-15oC to gives Stage-1 Compound.

Stage-2 : Stage-1 compound reacts with Sulfuryl Chloride and Pyridine in presence of Toluene at -15 to -10oC for 5 hrs, after reaction complies. Take organic layer give water washings. Distill out Toluene. Add Tetrahydrofuran in above residue. This layer reacts with Ammonia solution. After reaction complies, filter the by product and distill out Tetrahydrofuran completely. After distillation add Isopropyl Alcohol and n-Hexane, cool to 0-5oC to gives final Topiramate product.

Flow Chart

D-Fructose Isopropyl Alcohol By-Product Sulfuric Acid Sol.Recovery Acetone Stage I Evaporation Loss Sodium Hydroxide Effluent n-Hexane Organic Residue Water

Stage-1 Toluene Sulfuryl Chloride Pyridine Sol.Recovery Ammonia Solution (25%) Stage II Evaporation Loss Tetrahydrofuran Effluent Isopropyl Alcohol Organic Residue n-Hexane Water

Topiramate

17 ANNEXURE - II

PRODUCT : Olanzapine

Description :

Stage-3 : Stage-2 Compound reacts with Stannous Chloride and Hydrochloric acid in presence of Isopropyl Alcohol reflux at 80-95oC for 20 hrs, after reaction complies filter it to gives Stage-3 Compound Crude material. The Crude Stage-3 Compound material purified in Methanol media to form Stage-3 Compound Pure.

Stage-4 : Stage-3 Compound reacts with N-Methyl Piperazine at 125 to 130oC for 10 hrs, after reaction complies, add water and filter it, to gives Olanzapine crude material. Take Olanzapine crude material add Methylene Dichloride and carbon, stir for 2 hrs filter it, distillout Methylene Dichloride to form final Olanzapine compound.

Flow Chart

Malanonitrile Propionaldehyde Sol.Recovery Sulfur Evaporation Loss Stage I Triethylamine Effluent Dimethylformamide Organic Residue Water

Stage-1 Ortho Fluoro Nitrobenzene Sol.Recovery Potassium Hydroxide Stage II Evaporation Loss Acetonitrile Effluent Water Organic Residue

Stage-2 Isopropyl Alcohol By-Product Stannous Chloride Sol.Recovery Stage III Hydrochloric Acid (35%) Evaporation Loss Methanol Effluent Water Organic Residue

Stage-3 N-Methyl Piperazine Sol.Recovery Methylene Dichloride Stage IV Evaporation Loss Carbon Effluent Water Spent Carbon

Olanzapine

18 ANNEXURE - II

PRODUCT : Amlodipine Besylate

Description :

Stage-1 : Phthalic Anhydride is reacted with 2-Amino ethanol to get Phthalimido alcohol.

Stage-2 : Phthalic alfohol is reacted with 4-Chloro ethyl aceto acetate to obtain Ethyl-4-[2-(1,3-dioxo-1,3-dihydro- 2 H- isonidol-2yl)ethoxy]-3-oxobutanoate.

Stage-3 : Ethyl-4-{[2-(1,3-dioxo-1,3-dihydro-2 H-isonidol-2yl)ethoxy]-3-oxobutanonate is condensed with 2- Chloro Benzaldehyde and the product obtained is reacted with Methyl Aceto Acetate and Ammonia to obtain Methyl ester which on condensation with Monomethyl amine gives Amlodipine Base.

Stage-4 : Amlodipine Base on condensation with Benzene Sulfonic acid gives Amlodipine Besylate.

Flow Chart

Phthalic Anhydride 2-Amino ethanol Stage I Effluent Water

Stage-1 Toluene Sol.Recovery 4-Chloroethyl acetoacetate Evaporation Loss Sodium Hydride (40%) Stage II Effluent Acetic Acid Organic Residue Hydrochloric Acid (35%) Process Emissions Water

Stage-2 2-Chloro Benzaldehyde Catalyst Methyl Aceto Acetate Sol.Recovery Liq.Ammonia (20%) Stage III Evaporation Loss Acetic Acid Effluent n-Hexane Organic Residue Monomethylamine (30%) Water

Amlodipine Base Benzene Sulfonic acid Sol.Recovery Water Evaporation Loss Stage IV Methanol Effluent Activated Carbon Organic Residue Ethyl Acetate Spent Carbon

Amlodipine Besylate

19 ANNEXURE - II

PRODUCT : Montelukast Sodium

Description :

Stage-1 : 7-Chloro Quinaldehyde is reacted with Isopthalaldehyde in presence of Acetic Anhydride solvent as Methanol at 133-135oC further cool to 25-30oC to get 3-[2-(7-Chloro-2-Quinolinyl) Ethenyl] Benzaldehyde. Stage-2 : 3-[2-(7-Chloro-2-quinolinyl) ethenyl] benzaldehyde is reacted with Vinyl magnesium Bromide in Tetrahydrofuran in presence of Toluene at 0-5oC to give 1-{3-[2-(7-Chloro-2-quinolinyl) vinyl]phenyl} prop-2-en-1- ol. Stage-3 : 1{3-[2-(7-Chloro-2-Quinolinyl) vinyl]Phenyl}prop-2-en-1-ol is reacted with Methyl iodobenzoate and Palladium acetate as a catalyst in presence of acetonitrile at 80-85oC further coool to 25-30oC to give 2-(3-{3-[2- (7-Chloro-2-quinolinyl) Vinyl] Phenyl}-3-oxo propyl) benzoic acid methyl ester. Stage-4 : 2-(3-{3-[2-(7-Chloro-2-Quinolinyl) vinyl] Phenyl}-3-Oxopropyl) benzoic acid methyl ester is reacted with Dipchloride in presence of Tetrahydrofuran at -5oC to 0oC to give 2-(3-{3-[2-(7-Chloro-2-quinolinyl)vinyl] phenyl}-3- hydroxy propyl) benzoic acid methyl ester. Stage-5 : 2-(3-{3-[2-(7-Chloro-2-Quinolinyl) vinyl] phenyl] 3-hydroxypropyl) benzoic acid methyl ester is reacted with Methyl Magnesium Chloride and Hydrochloric Acid at -5oC to 0oC, further crystallized with Isopropyl Ether to give 1-{3-[2-(7-Chloro-2-quinolinyl)vinyl]phenyl}-3-[2-(1-Hydroxy-1-methyl ethyl) Phenyl] Propan-1-ol.

Stage-6 : 1-{3-[2-(7-Chloro-2-quinolinyl)vinyl]phenyl}-3-[2-(1-Hydroxy-1-methyl ethyl) Phenyl] Propan-1-ol is reacted with Methane Sulfonylchloride in presence of Diisopropylamine, Toluene and Acetonitirle as a solvent media to give Methane Sulfonic acid -1-{3-[2-(7-Chloro-2-quinolinyl)vinyl]phenyl}-3-[2-(1-hydroxy-1-methyl ethyl) phenyl] propyl ester. Stage-7 : Methane Sulfonic acid-1-{3-[2-(7-Chloro-2-quinolinyl)vinyl]phenyl}-3-[2-(1-hydroxy-1-mehtyl ethyl)phenyl] Propyl ester is reacted with (1-Mercaptomethyl cyclopropyl) acetic acid in presence of Tetrahydrofuran and ethyl acetate to give Montelukast. Stage-8 : Montelukast is reacted with Dicyclohexylamine in presence of EthylAcetate and n-Hexane to give Montelukast Dicyclohexylamine.

Stage-9 : Montelukast Dicyclohexylamine is reacted with Acetic acid to get Montelukast free acid. Montelukast free acid then reacted with Sodium Hydroxide in presence of Toluene and n-Hexane to get Montelukast Sodium.

20 ANNEXURE - II

PRODUCT : Montelukast Sodium

Flow Chart

7-Chloro quinaldehyde Methanol Sol.Recovery Stage I Isophthaladehyde Evaporation Loss Acetic Anhydride Organic Residue

Stage-1 Toluene Sol.Recovery Vinyl Magnesium Bromide in Stage II Evaporation Loss Tetrahydrofuran (40%) Effluent Water Organic Residue

Stage-2 Methyl Iodobenzoate Sol.Recovery Catalyst Evaporation Loss Stage III Sodium Hydroxide Effluent Acetonitrile Organic Residue Water

Stage-3 By-Product DIP Chloride Sol.Recovery Tetrahydrofuran Evaporation Loss Stage IV Water Effluent Organic Residue Process Emissions

Stage-4 Methyl Magnesium Chloride in Tetrahydrofuran (25%) Sol.Recovery t-Butanol Stage V Evaporation Loss Isopropyl ether Effluent Hydrochloric Acid (35%) Organic Residue Water

21 ANNEXURE - II

PRODUCT : Montelukast Sodium

Flow Chart

Stage-5 Toluene Sol.Recovery Acetonitrile Stage VI Evaporation Loss Diisopropylamine Organic Residue Methane Sulfonyl Chloride

Stage-6 Tetrahydrofuran (1-Mercaptomethyl cyclo propyl) acetic acid Sol.Recovery n-Butyllithium in Cyclohexane Stage VII Evaporation Loss (15%) Effluent Ethyl Acetate Organic Residue Sodium Chloride (10%) Tartaric acid (5%)

Stage-7 Ethyl Acetate Sol.Recovery StageVIII Dicyclohexylamine Evaporation Loss n-Hexane Organic Residue

Stage-8 Toluene Water Sol.Recovery Acetic Acid Stage IX Evaporation Loss Sodium Hydroxide in Methanol Effluent (50%) Organic Residue n-Hexane

Montelukast Sodium

22 ANNEXURE - II

PRODUCT : Loratadine

Description :

Stage-1 : Methyl Nicotinate reacts with m-Chlorobenzylcyanide in the presence of Sodium Methoxide in solvent media to get Stage-1 intermediate.

Stage-2 : Stage-1 intermediate hydrolysis in the presence of Hydrochloric Acid in Toluene solvent media to get Stage-2 intermediate.

Stage-3 : Stage-2 intermediate reacts with Hydrazine hydrate in the presence of Monoethylene glycol to get Stage- 3 intermediate. Stage-4 : Stage-3 intermediate reacts with Hydrogen Peroxide in presence of Chloroform solvent media to get Stage-4 intermediate. Stage-5 : Stage-4 intermediate reacts with Sodium cyanide in presence of Hydrochloric Acid in Chloroform solvent media to get Stage-5 intermediate. Stage-6 : Stage-5 intermediate reacts with Potassium Hydroxide in the presence of Hydrochloric Acid in Butanol solvent media to get Stage-6 intermediate.

Stage-7 : Stage-6 intermediate reacts with Phosphorus Pentachloride in the presence of Toluene and Methylene Dichloride solvent media to get Stage-7 intermediate. Stage-8 : Stage-7 intermediate reacts with N-Methyl chloro piperidine and Magnesium in presence of Water in Toluene solvent media to get Stage-8 intermediate. Stage-9 : Stage-8 intermediate under goes dehydrolysis in the presence of Sulfuric Acid in Toluene solvent media to give Stage-9 intermediate. Stage-10 : Stage-9 intermediate reacts with Ethyl chloroformate in presence of Triethylamine base in Tetrahydrofuran solvent media to get Loratadine.

23 ANNEXURE - II

PRODUCT : Loratadine

Flow Chart

Methyl Nicotinate m-Chlorobenzyl cyanide Sol.Recovery Sodium Methoxide Stage I Evaporation Loss Methanol Effluent Ice water

Stage-1 Hydrochloric Acid (35%) Sol.Recovery Ammonia (25%) Solution Stage II Evaporation Loss Toluene Effluent Water Process Emissions

Stage-2 Hydrazine hydrate (80%) Effluent Stage III Sodium Hydroxide Organic Residue Monoethylene glycol Process Emissions

Stage-3 Methanol Acetic Acid Hydrogen Peroxide (50%) Sol.Recovery Stage IV Ammonia (25%) Solution Evaporation Loss Chloroform Effluent Sodium Tungstate Water

Stage-4 Chloroform Sol.Recovery Sodium Cyanide Evaporation Loss Stage V Hydrochloric Acid (35%) Effluent Isopropyl Alcohol Organic Residue Water

24 ANNEXURE - II

PRODUCT : Loratadine

Flow Chart

Stage-5 Potassium Hydroxide Sol.Recovery Butanol Stage VI Evaporation Loss Hydrochloric Acid (35%) Effluent Water Process Emissions

Stage-6 Methylene Dichloride Phosphorus Pentachloride Sol.Recovery Aluminum Chloride Evaporation Loss Sodium Hydroxide (40%) Stage VII Effluent Solution Organic Residue Toluene Process Emissions Hydrochloric Acid (35%) Water

Stage-7 N-Methyl chloro piperidine Magnesium Sol.Recovery Tetrahydrofuran Evaporation Loss StageVIII Lithium Bromide Effluent Ammonium Chloride Organic Residue Toluene Inorgainc Solid Waste Water

Stage-8 Sulfuric Acid Ammonia (25%) Solution Sol.Recovery Stage IX Toluene Evaporation Loss Sodium Sulfate Effluent Water

Stage-9 Ethyl Chloroformate Sol.Recovery Triethylamine Stage X Evaporation Loss Tetrahydrofuran Effluent Water Process Emissions

Loratadine

25 ANNEXURE - II

PRODUCT : Valsartan

Description :

Stage-1 : 2-Cyano biphenyl-4-carboxaldehyde on reacting with Methyl-L-Valinate Hydrochloride in presence of Potassium Carbonate as a base and Acetonitrile solvent media and it is further on reductive amination with Hydrogen gives Methyl-N-[(2-Cyano biphenyl-4-yl) methyl]-L-valinate. Stage-2 : Methyl-N-[(2-Cyano biphenyl-4-yl) methyl]-L-valinate on treatment with Valeryl chloride in presence of Triethylamine base and Toluene solvent media gives Methyl-N-Valeryl-N-[(2-Cyano biphenyl-4- yl) methyl]-L- valinate.

Stage-3 : Methyl-N-Valeryl-N-[(2-Cyano biphenyl-4-yl) methyl]-L-valinate on treatment with Tributyl tinazide in presence of Acetone and Ethyl Acetate solvent media gives Valsartan.

Flow Chart

2-Cyano biphenyel-4- carboxaldehyde Methyl-L-Valinate Sol.Recovery Hydrochloride Evaporation Loss Stage I Potassium Carbonate Effluent Acetonitrile Organic Residue Hydrogen Process Emissions Water

Stage-1 Valeryl Chloride Sol.Recovery Triethylamine Stage II Evaporation Loss Toluene Effluent Water Organic Residue

Stage-2 Tributyl tinazide Acetone Sol.Recovery Sulfuric Acid Evaporation Loss Stage III Sodium Hydroxide Effluent Ammonium Sulfate Organic Residue Ethyl Acetate Water

Valsartan

26 ANNEXURE - II

PRODUCT : Clopidogrel Hydrogensulfate

Description :

Stage-1 : Take Methanol, add 2-Chlorophenyl Glycine and feed Sulfuric acid below 15oC. Heat to 60-65oC and maintaine for 20 hrs. Distill off solvent completely and add Toluene and distill off Toluene to remove the Methanol traces. Cool to residue to room temp. and add water. Stir to dissolve and add Methylene Dichloride. Adjust pH (neutral) with aq. Ammonia and separate layers. Distill of Methylene Dichloride complelty to get crude Stage-1 product. Stage-2 : Take Methanol, add Stage-1 and add L-Tartaric acid. Stir for 20 hrs at room temp. Centrifuge the material. Dry the product at 50-60oC. Take Methanol Mls and distill off solvent completely. Add water to the residue and adjust pH with Aq. Ammonia (to neutral pH). Extract with Methylene Dichloride. Distill off solvent completely to get recovered Stage-2.

Stage-3 : Take water and add Sodium Hydroxide flakes. Stir to dissolve and cool to room temp. Add 2- Thiophene Ethanol and Toluene lot-1 mixture. Cool to below 10oC. Feed mixture of P-Toluene Sulfonyl Chloride and Toluene lot-2 below 10oC and maintian for 1 hr. Separate layers and wash organic layer with water lot-2 and 3. Distill off solvent to get Stage-3 product. Stage-4 : Take water lot-1 and add Stage-2. Add Toluene and adjust pH with Aq. Ammonia to neutral. Separate layers. Distill off Toluene completely. Add Stage-3 and Potassium Bicarbonate. Heat and maintaine at 80-85o for 48 hrs. Cool to room temperature and add water lot-2 stir to dissolve. Add Ethyl Acetate separate layers. Wash organic layer with water lot-3 add Hydrochloric Acid to organic layer below 15oC. Centrifuge the material and dry the Stage-4 product at 50-60oC. Stage-5 : Take Toluene and add Stage-4 Crude. Heat to 50-55oC and maintaine for 1hrs. Cool to room temperature and centrifuge the material. Dry the Stage-5 pure product at 60-65oC. Collect Mls and distill off Toluene to get reccovered Toluene. Stage-6 : Take water lot-1, Stage-5 in reactor. Add Formalin solution at room temperature. Heat and maintain at 50-55oC till reaction completion. Cool to room temperature and charge water lot-2 and Toluene lot-1. Add Sodium Hydroxide separate Toluene layer. Extract aq.layer with Toluene lot-2. Combine Toluene layers and distill off solvent to get Clopidogrel base. Stage-7 : Take Acetone lot-1 in reactor, add Clopidogrel base and cool to below 10oC. Feed Sulfuric Acid below 10oC. Maintain for 1 to 1.5 hrs below 10oC. Raise temperature and maintain at room temperature for 20-24 hrs. Filter the Clopidogrel Hydrogensulfate product and wash with Acetone lot-2. Dry the Clopidogrel Hydrogensulfate product below 40oC for 6-8 hrs.

27 ANNEXURE - II

PRODUCT : Clopidogrel Hydrogensulfate

Flow Chart

2-Chlorophenyl Glycine Methanol Sulfuric Acid Sol.Recovery Toluene Stage I Evaporation Loss Methylene Dichloride Effluent Ammonia (25%) solution Organic Residue Water

Stage-1 Methanol Sol.Recovery L-Tartaric Acid Evaporation Loss Stage II Methylene Dichloride Effluent Ammonia (25%) solution Organic Residue Water

2-Thiophene Ethanol P-Toluene Sulfonyl Chloride Sodium Hydroxide Sol.Recovery Toluene Stage III Evaporation Loss Hydrochloric Acid (35%) Effluent Water Organic Residue

Stage-2 Ammonia (25%) solution Stage-3 Sol.Recovery Potassium Bicarbonate Evaporation Loss Stage IV Toluene Effluent Ethyl Acetate Organic Residue Hydrochloric Acid (35%) Process Emissions Water

Stage-4 (Crude) Sol.Recovery Toluene Stage V Evaporation Loss Organic Residue

28 ANNEXURE - II

PRODUCT : Clopidogrel Hydrogensulfate

Flow Chart

Stage-5 (Pure) Formalin (37%) Sol.Recovery Sodium Hydroxide Stage VI Evaporation Loss Toluene Effluent Water Organic Residue

Clopidogrel Base Sol.Recovery Acetone Stage VII Evaporation Loss Sulfuric Acid Organic Residue

Clopidogrel Hydrogensulfate

29 ANNEXURE - II

PRODUCT : Gabapentin

Description :

Stage-1 : This stage invloves the reaction of 1,1-Cyclohexane diacetic acid with Acetic Anhydride to give 1,1- Cyclohexane diacetic acid anhydride.

Stage-2 : 1,1-Cyclohexane diacetic acid anhydride obtained in stage-1 is treated with Hydroxylamine Hydrochloride in presence of Sodium Carbonate to get 1,1-Cyclohexane diacetic acid N-Hydroxyimide.

Stage-3 : This stage invloves the reaction of 1,1-Cyclohexane diacetic acid N-Hdyroxyimide with Benzene Sulfonyl Chloride in presence of Sodium Carbonate to give N-Benzene sulfonyloxy-1,1-Cyclohexane diacetic acid imide.

Stage-4 : The N-Benzene sulfonyloxy-1,1-Cyclohexane diacetic acid imide derivative obtained in Stage-3 is subjected to Lossen rearrangement by boiling in 10% Sodium Hydroxide solution, followed by pH adjustment with Hydrochloric Acid in presence of Ethanol to give the Gabapentin product.

Flow Chart

1,1-Cyclohexane diacetic acid Sol.Recovery Acetic Anhydride Stage I Evaporation Loss Effluent

Stage-1 Hydroxylamine Hydrochloride Effluent Stage II Sodium Carbonate Process Emissions Water

Stage-2 Sodium Carbonate (10%) Effluent Stage III Benzene Sulfonyl Chloride Process Emissions Water

Stage-3 Sol.Recovery Sodium Hydroxide (10%) Evaporation Loss Stage IV Hydrochloric Acid (35%) Effluent Ethanol Process Emissions

Gabapentin

30 ANNEXURE - II

PRODUCT : 5-Amino-1-cyclopropyl-6,7,8-trifluoro-4-oxo-1,4-dihydro- quinoline-3-carboxylic acid ethyl ester

Description :

Stage-3 : Q-Ester on condensation with Benzylamine in presence of Triethylamine gives Benzyl Compound.

Stage-4 : Benzyl Compound on reduction with Hydrogen on Palladium Carbon gives 5-Amino-1-cyclopropyl- 6,7,8-trifluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid ethyl ester.

31 ANNEXURE - II

PRODUCT : 5-Amino-1-cyclopropyl-6,7,8-trifluoro-4-oxo-1,4-dihydro- quinoline-3-carboxylic acid ethyl ester

Flow Chart

Stage-1 Triethyl Orthoformate Sol.Recovery Acetic Acid Evaporation Loss Cyclopropylamine Stage II Effluent Toluene Organic Residue Potassium Carbonate Process Emissions Water

Stage-2 Benzylamine Sol.Recovery Potassium Hydroxide Stage III Evaporation Loss Toluene Effluent Water Organic Residue

Stage-3 Sol.Recovery Carbon Evaporation Loss Methanol Effluent Stage IV Hydrogen Organic Residue Hyflo Spent Carbon Water Process Emissions

5-Amino-1-cyclopropyl-6,7,8-trifluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid ethyl ester

32 ANNEXURE - II

PRODUCT : 2-(4-Methyl-2-phenyl piperazin-1-yl) pyridine-3-carboxylic acid

Description :

Stage-1 : 1-Methyl-3-phenyl piperazine is condensed with 2-Chloro nicotinonitrile in Dimethylformamide in presence of Sodium Hydroxide and Potassium Fluoride to obtain Mirtazapine Stage-I material.

Stage-2 : Hydrolysis of Mirtazapine Stage-I material with Sodium Hydroxide and Hydrochloric Acid in presence of Toluene, Methylene Dichloride and Ethanol solvent media gives 2-(4-Methyl-2-phenyl piperazin-1-yl) pyridine-3- carboxylic acid.

Flow Chart

Stage-1 Toluene Sol.Recovery Methylene Dichloride Evaporation Loss Ethanol Stage II Effluent Sodium Hydroxide Organic Residue Hydrochloric Acid (35%) Process Emissions Water

2-(4-Methyl-2-phenyl piperazin-1-yl) pyridine-3-carboxylic acid

33 ANNEXURE - II

PRODUCT : 2,3:4,5-Bis-O-(1-Methyl ethylidene)-b-Fructopyranose

Description :

Flow Chart

D-Fructose Isopropyl Alcohol By-Product Sulfuric Acid Sol.Recovery Acetone Stage I Evaporation Loss Sodium Hydroxide Effluent n-Hexane Organic Residue Water

2,3:4,5-Bis-O-(1-Methyl ethylidene)-b-Fructopyranose

34 ANNEXURE - II

PRODUCT : 2-Methyl-4-amino-10H-thieno[2,3-b][1,5] benzodiazepine Hydrochloride

Description :

Stage-1 : Malanonitrile reacts with Propionaldehyde and Sulfur in presence of Triethylamine and Dimethylformamide at 0-5oC for 15 hrs. After reaction complies filter it to gives Stage-1 Compound. Stage-2 : Stage-1 Compound reacts with Ortho Fluoro Nitrobenzene in presence of Acetonitrile and Potassium Hydroxide at 20-40oC for 12 hrs to gives Stage-2 Compound. Stage-3 : Stage-2 Compound reacts with Stannous Chloride and Hydrochloric acid in presence of Isopropyl Alcohol reflux at 80-95oC for 20 hrs, after reaction complies filter it to gives Stage-3 Compound Crude material. The Crude Stage-3 Compound material purified in Methanol media to form 2-Methyl-4-amino-10H-thieno [2,3- b][1,5] benzodiazepine Hydrochloride.

Flow Chart

Malanonitrile Propionaldehyde Sol.Recovery Sulfur Evaporation Loss Stage I Triethylamine Effluent Dimethylformamide Organic Residue Water

Stage-1 Ortho Fluoro Nitrobenzene Sol.Recovery Potassium Hydroxide Stage II Evaporation Loss Acetonitrile Effluent Water Organic Residue

Stage-2 Isopropyl Alcohol By-Product Stannous Chloride Sol.Recovery Stage III Hydrochloric Acid (35%) Evaporation Loss Methanol Effluent Water Organic Residue

2-Methyl-4-amino-10H-thieno[2,3-b][1,5] benzodiazepine Hydrochloride

35 ANNEXURE - II

PRODUCT : Ethyl-4-[2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)-ethoxy]-3- oxobutanoate

Description :

Stage-1 : Phthalic Anhydride is reacted with 2-Amino ethanol to get Phthalimido alcohol.

Stage-2 : Phthalic alfohol is reacted with 4-Chloro ethyl aceto acetate to obtain Ethyl-4-[2-(1,3-dioxo-1,3-dihydro- 2 H- isonidol-2yl)ethoxy]-3-oxobutanoate.

Flow Chart

Phthalic Anhydride 2-Amino ethanol Stage I Effluent Water

Stage-1 Toluene Sol.Recovery 4-Chloroethyl acetoacetate Evaporation Loss Sodium Hydride (40%) Stage II Effluent Acetic Acid Organic Residue Hydrochloric Acid (35%) Process Emissions Water

Ethyl-4-[2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)-ethoxy]-3-oxobutanoate

36 ANNEXURE - II

PRODUCT : (E)-2-(3-{3-[2-(7-Chloro-2-quinolinyl) vinyl] phenyl}-3-oxo propyl) benzoic acid methyl ester

Description :

Flow Chart

7-Chloro quinaldehyde Methanol Sol.Recovery Stage I Isophthaladehyde Evaporation Loss Acetic Anhydride Organic Residue

Stage-1 Toluene Sol.Recovery Vinyl Magnesium Bromide in Stage II Evaporation Loss Tetrahydrofuran (40%) Effluent Water Organic Residue

Stage-2 Methyl Iodobenzoate Sol.Recovery Catalyst Evaporation Loss Stage III Sodium Hydroxide Effluent Acetonitrile Organic Residue Water

(E)-2-(3-{3-[2-(7-Chloro-2-quinolinyl) vinyl] phenyl}-3-oxo propyl) benzoic acid methyl ester

37 ANNEXURE - II

PRODUCT : N-[(2-Cyano-(1,1'-biphenyl)-4-yl) methyl] valine methyl ester

Description :

Flow Chart

2-Cyano biphenyel-4- carboxaldehyde Methyl-L-Valinate Sol.Recovery Hydrochloride Evaporation Loss Stage I Potassium Carbonate Effluent Acetonitrile Organic Residue Hydrogen Process Emissions Water

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

38 ANNEXURE - II

PRODUCT : (+)-2-(2-Chlorophenyl)-N-(2-thienyl) ethyl) glycine methyl ester hydrochloride

Description :

39 ANNEXURE - II

PRODUCT : (+)-2-(2-Chlorophenyl)-N-(2-thienyl) ethyl) glycine methyl ester hydrochloride

Flow Chart

2-Chlorophenyl Glycine Methanol Sulfuric Acid Sol.Recovery Toluene Stage I Evaporation Loss Methylene Dichloride Effluent Ammonia (25%) solution Organic Residue Water

Stage-1 Methanol Sol.Recovery L-Tartaric Acid Evaporation Loss Stage II Methylene Dichloride Effluent Ammonia (25%) solution Organic Residue Water

2-Thiophene Ethanol P-Toluene Sulfonyl Chloride Sodium Hydroxide Sol.Recovery Toluene Stage III Evaporation Loss Hydrochloric Acid (35%) Effluent Water Organic Residue

Stage-2 Ammonia (25%) solution Stage-3 Sol.Recovery Potassium Bicarbonate Evaporation Loss Stage IV Toluene Effluent Ethyl Acetate Organic Residue Hydrochloric Acid (35%) Process Emissions Water

(+)-2-(2-Chlorophenyl)-N-(2- thienyl) ethyl) glycine methyl Sol.Recovery Stage V ester hydrochloride (Crude) Evaporation Loss Toluene Organic Residue

(+)-2-(2-Chlorophenyl)-N-(2-thienyl) ethyl) glycine methyl ester hydrochloride

40 ANNEXURE - II

PRODUCT : Dabigatran Etexilate Mesylate

Description :

Stage-1 : 4-Chloro-3-Nitrobenzoic acid reacts with Methylamine in presence of Acetic acid in Isopropyl Alcohol solvent medium to get Stage-1 Compound.

Stage-2 : 2-Aminopyridine on reaction with Ethyl Propionate in presence of Hydrochloric acid and Ammonia in Chloroform and n-Hexane solvent media to give Stage-2 Intermediate.

Stage-3 : 4-Aminobenzonitrile reacts with Bromoacetic acid in presence of Sodium Hydroxide in Ethyl Acetate sovent medium to form Stage-3 Compound.

Stage-4 : Stage-1 Compound on reaction with Stage-2 Intermediate in presence of Oxalyl Chloride, Sodium Hydroxide and Triethylamine in Toluene and Ethanol solvent media to get Stage-4 Product.

Stage-5 : Stage-4 Product on reduction with Hydrogen in presence of Ammonia in Ethyl Acetate solvent medium to get Stage-5 Compound.

Stage-6 : Stage-5 Compound gets reacted with Stage-3 Compound in presence of Carbonyldiimidazole, Acetic acid and Ammonia in Methylene Dichloride, Ethyl Acetate, Dimethylformamide and Acetone solvent media to form Stage-6 Intermediate.

Stage-7 : Stage-6 Intermediate on reaction with Ammonium Carbonate in presence of Hydrochloric acid and Sulfuric acid in Ethanol and Ethyl Acetate solvent media to form Stage-7 Product.

Stage-8 : Stage-7 Product reacts with Hexyl Cabonochloridate in presence of Methanesulfonic acid and Triethylamine in Chloroform and Ethyl Acetate solvent media to form Dabigatran Etexilate Mesylate.

41 ANNEXURE - II

PRODUCT : Dabigatran Etexilate Mesylate

Flow Chart

4-Chloro-3-Nitrobenzoic acid Methylamine (40%) Sol.Recovery Isopropyl Alcohol Stage I Evaporation Loss Acetic acid Effluent Water

2-Aminopyridine Ethyl Propionate Sol.Recovery Hydrochloric acid (35%) Evaporation Loss Chloroform Stage II Effluent Ammonia (25%) Solution Organic Residue n-Hexane Process Emissions Water

4-Aminobenzonitrile Bromoacetic acid Sol.Recovery Ethyl Acetate Stage III Evaporation Loss Sodium Hydroxide Effluent Water

Stage-1 Stage-2 Oxalyl Chloride Sol.Recovery Toluene Evaporation Loss Stage IV Triethylamine Effluent Ethanol Organic Residue Sodium Hydroxide Water

Stage-4 Ammonia (25%) Solution Sol.Recovery Ethyl Acetate Evaporation Loss Stage V Raney Nickel Effluent Hydrogen Organic Residue Water Process Emissions

42 ANNEXURE - II

PRODUCT : Dabigatran Etexilate Mesylate

Flow Chart

Stage-5 Methylene Dichloride Ethyl Acetate Dimethylformamide Sol.Recovery Stage-3 Evaporation Loss Stage VI Carbonyldiimidazole Effluent Acetic acid Organic Residue Acetone Process Emissions Ammonia (25%) Solution Water

Stage-6 Sol.Recovery Ethanol Evaporation Loss Ethyl Acetate Effluent Stage VII Ammonium Carbonate Organic Residue Hydrochloric acid (35%) Inorgainc Solid Waste Sulfuric acid Process Emissions

Stage-7 Hexyl Cabonochloridate Chloroform Sol.Recovery Triethylamine StageVIII Evaporation Loss Ethyl Acetate Effluent Methanesulfonic acid Organic Residue Water

Dabigatran Etexilate Mesylate

43 ANNEXURE - II

PRODUCT : Domperidone

Description :

Stage-1 : Monomethylamine reacts with Methyl Acrylate in Methanol solvent medium to form Stage-1 Compound.

Stage-2 : Stage-1 Compound on reaction with Sodium Methoxide in aqueous medium to get Stage-2 Intermediate.

Stage-3 : Stage-2 Intermediate on hydrolysis in presence of Chloroform solvent medium give Stage-3 Compound.

Stage-4 : Stage-3 Compound on reaction with Ethyl Chloroformate in presence of Sodium Hydroxide in Toluene solvent medium to get Stage-4 Intermediate. .

Stage-5 : Stage-4 Intermediate on hydrolysis in presence of Ammonia in Methanol solvent medium to form Stage-5 Compound.

Stage-6 : Stage-5 Compound gets reacted with 2,5-Dichloronitrobenzene in presence of Sodium Hydroxide and Potassium Iodide in aqueous medium to give Stage-6 Product.

Stage-7 : Stage-6 Product on hydrolysis in presence of Toluene and Methanol solvent media to get Stage-7 Intermediate.

Stage-8 : Stage-7 Intermediate is on reaction with Urea in presence of Hydrochloric acid and Ammonia in aqueous medium and gets purified with Carbon to form Stage-8 Compound.

Stage-9 : o-Phenyldiamine gets reacted with Methyl Acetoacetate in presence of Sodium Hydroxide and Hydrochloric acid in o-Xylene solvent medium to give Stage-9 Intermediate.

Stage-10 : Stage-9 Intermediate is on reaction with 1-Bromo-3-Chloropropane in presence of Sodium Hydroxide and Tetrabutylammonium Bromide in aqueous medium to get Stage-10 Compound.

Stage-11 : Stage-10 Compound on hydrolysis in presence of Ammonia and Hydrochloric acid in Methanol solvent medium to form Stage-11 Intermediate.

Stage-12 : Stage-9 Intermediate on condensation with Stage-11 Intermediate in presence of Sodium Hydroxide, Ammonium Chloride, Acetic acid and Ammonia in Methanol sovlent medium and gets purified with Carbon to obtain Domperidone.

44 ANNEXURE - II

PRODUCT : Domperidone

Flow Chart

Monomethylamine Sol.Recovery Methyl Acrylate Stage I Evaporation Loss Methanol Organic Residue

Stage-1 Sol.Recovery Sodium Methoxide Evaporation Loss Water Stage II Organic Residue Inorganic Solid Waste Process Emissions

Stage-2 Sol.Recovery Chloroform Stage III Evaporation Loss Water Effluent

Stage-3 Toluene Sol.Recovery Ethyl Chloroformate Stage IV Evaporation Loss Sodium Hydroxide (40%) Effluent Water Organic Residue

Stage-4 Sol.Recovery Methanol Evaporation Loss Ammonia Stage V Effluent Hydrogen Organic Residue Raney Nickel Process Emissions

Stage-5 2,5-Dichloronitrobenzene Sodium Hydroxide (40%) Stage VI Effluent Potassium Iodide Water

Stage-6 Sol.Recovery Hydrogen Evaporation Loss Toluene Stage VII Effluent Methanol Organic Residue Raney Nickel Process Emissions

45 ANNEXURE - II

PRODUCT : Domperidone

Flow Chart

Stage-7 Urea Hydrochloric acid (35%) Effluent StageVIII Carbon Spent Carbon Ammonia (15%) Solution Water o-Phenyldiamine Methyl Acetoacetate o-Xylene Sol.Recovery Stage IX Sodium Hydroxide (40%) Evaporation Loss Hydrochloric acid (35%) Effluent Water

Stage-9 1-Bromo-3-Chloropropane Sodium Hydroxide (40%) Stage X Effluent Tetrabutylammonium Bromide Water

Stage-10 Sol.Recovery Methanol Evaporation Loss Stage XI Ammonia (10%) Solution Effluent Hydrochloric acid (15%) Organic Residue

Stage-8 Stage-11 Sodium Hydroxide (40%) Sol.Recovery Ammonium Chloride Evaporation Loss Acetic acid Stage XII Effluent Methanol Organic Residue Ammonia (25%) Solution Spent Carbon Carbon Water

Domperidone

46 ANNEXURE - II

PRODUCT : Irbesartan

Description :

Stage-1 : Cyclopentanone on reaction with Sodium Cyanide in presence of Ammonium Chloride and Ammonia in Methanol and Methylene Dichloride solvent media to get Stage-1 Compound.

Stage-2 : Stage-1 Compound on reaction with Valeryl Chloride in presence of Sodium Bicarbonate in Methylene Dichloride solvent medium to form Stage-2 Intermediate.

Stage-3 : Stage-2 Intermediate on reaction with Hydrogen Chloride which is purged in Isobutanol in presence of Isopropyl Alcohol solvent medium to form Stage-3 Compound.

Stage-4 : 2-Cyano-4-methyl byphenyl on reaction with N-Bromo Succinimide in presence of Azoisobutironitrile in Methylene Dichloride solvent medium to get Stage-4 Product.

Stage-5 : Stage-4 Product on condensation with Stage-2 Intermediate in presence of Potassium Hydroxide and Tetrabutylammonium Bromide in Methylene Dichloride solvent medium to form Stage-5 Compound.

Stage-6 : Stage-5 Compound on reaction with Sodium Azide in presence of Tributytin Azide and Sodium Hydroxide in o-Xylene and Ethyl Acetate solvent media to obtain Irbesartan.

47 ANNEXURE - II

PRODUCT : Irbesartan

Flow Chart

Cyclopentanone Sodium Cyanide Ammonium Chloride Sol.Recovery Methanol Stage I Evaporation Loss Ammonia (25%) Solution Effluent Methylene Dichloride Organic Residue Water

Stage-l Sol.Recovery Sodium Bicarbonate Evaporation Loss Valeryl Chloride Stage II Effluent Methylene Dichloride Organic Residue Water Process Emissions

Stage-2 Isobutanol Sol.Recovery Stage III Isobutanol Hydrochloride (5%) Evaporation Loss Isopropyl Alcohol Organic Residue

2-Cyano-4-methyl byphenyl Methylene Dichloride Sol.Recovery Azoisobutironitrile Stage IV Evaporation Loss N-Bromo Succinimide Effluent Water Organic Residue

Stage-4 Stage-2 Sol.Recovery Methylene Dichloride Evaporation Loss Stage V Potassium Hydroxide Effluent Tetrabutylammonium Bromide Organic Residue Water

Stage-5 o-Xylene Sodium Azide Sol.Recovery Tributytin Azide Stage VI Evaporation Loss Sodium Hydroxide Effluent Ethyl Acetate Organic Residue Water

Irbesartan

48 ANNEXURE - II

PRODUCT : Losartan Potassium

Description :

Stage-1 : 2-Cyano-4-methyl byphenyl reacts with N-Bromo Succinimide in presence of Azoisobutironitrile in Methylene Dichloride solvent medium to get Stage-1 Compound.

Stage-2 : Valeronitrile gets reacted with Methanol in presence of Hydrochloric acid, Sodium Hydroxide and Sulfuric acid in Toluene solvent medium to give Stage-2 Intermediate.

Stage-3 : Stage-2 Intermediate is react with Aminoacetic acid in presence of Toluene and Methanol solvent media to form Stage-3 Compound. Stage-4 : Stage-3 Compound on reaction with Phosphorous Oxychloride in presence of Sodium Hydroxide, Acetic acid and Dimethylformamide in Methanol and Toluene solvent media and gets purified with Carbon to get Stage-4 Product. Stage-5 : Stage-4 Product reacts with Stage-1 Compound in presence of Sodium Borohydride, Sodium Hydroxide, and Tetrabutylammonium Bromide in Toluene solvent medium to form Stage-5 Compound.

Stage-6 : Stage-5 Compound on reaction with Sodium Azide in presence of Potassium Hydroxide, Sodium Matabisulfate, Triethylamine Hydrochloride and Hydrochloric acid in Toluene, Ethyl Acetate and Isopropyl Alcohol solvent media to obtain Losartan Potassium.

49 ANNEXURE - II

PRODUCT : Losartan Potassium

Flow Chart

2-Cyano-4-methyl byphenyl Methylene Dichloride Sol.Recovery Azoisobutironitrile Stage I Evaporation Loss N-Bromo Succinimide Effluent Water Organic Residue

Valeronitrile Methanol Hydrochloric acid (35%) Sol.Recovery Sulfuric acid Stage II Evaporation Loss Toluene Effluent Sodium Hydroxide (40%) Organic Residue Water

Stage-2 Toluene Sol.Recovery Aminoacetic acid Stage III Evaporation Loss Methanol Effluent Water Organic Residue

Stage-3 Phosphorous Oxychloride Dimethylformamide Sol.Recovery Sodium Hydroxide (40%) Evaporation Loss Methanol Stage IV Effluent Toluene Organic Residue Carbon Spent Carbon #REF! Water

Stage-4 Stage-1 Sol.Recovery Toluene Evaporation Loss Sodium Hydroxide Stage V Effluent Tetrabutylammonium Bromide Organic Residue Sodium Borohydride Process Emissions Water

50 ANNEXURE - II

PRODUCT : Losartan Potassium

Flow Chart

Stage-5 Toluene Triethylamine Hydrochloride Sodium Azide Sol.Recovery Sodium Matabisulfate Evaporation Loss Potassium Hydroxide Stage VI Effluent Carbon Organic Residue Hydrochloric acid (35%) Spent Carbon Ethyl Acetate Isopropyl Alcohol Water

Losartan Potassium

51 ANNEXURE - II

PRODUCT : Olmesartan Medoxomil

Description :

Stage-1 : 2-Cyano-4-methyl biphenyl on reaction with Sodium Azide in presence of Sulfuric acid, Sodium Nitrate and Triethylamine Hydrochloride in Toluene solvent medium to form Stage-1 Compound.

Stage-2 : Stage-1 Compound reacts with Trityl Chloride in presence of Triethylamine in Methylene Dichloride and Methanol solvent media to get Stage-2 Intermediate.

Stage-3 : Stage-2 Intermediate is react with N-Bromo Succinimide in presence of Sodium Metabisulfate and Azobisisobutyronitrile in Methylene Dichloride and Ethyl Acetate solvent media to give Stage-3 Compound.

Stage-4 : Diethyl taratrate on rection with Ammonium Acetate in presence of Butyraldehyde, Acetic acid, Sodium Hydroxide, N-Bromo Succinimide and Azoisobutyronitrile in Tetrahydrofuran solvent medium to get Stage-4 Intermediate.

Stage-5 : Stage-4 Intermediate on reaction with Methyl Magesium Chloride in presence of Hydrochloric acid and Sodium Chloride in Toluene and Tetrahydrofuran solvent media to form Stage-5 Product.

Stage-6 : Stage-5 Product on condensation with Stage-3 Compound in presence of Tetrabutylammonium Bromide and Sodium Hydroxide in Acetone and Methanol solvent media to get Stage-6 Compound.

Stage-7 : Stage-6 Compound reacts with 4-(Chloromethyl)-5-methyl-1,3-dioxol-2-one in presence of Triethylamine in Dimethylacetimide and Methanol solvent media to obtain Stage-7 Intermediate.

Stage-8 : Stage-7 Intermediate on hydrolysis in presence of Acetic acid and Isopropyl Alcohol solvent media to form Olemisartan Medoxomil.

52 ANNEXURE - II

PRODUCT : Olmesartan Medoxomil

Flow Chart

2-Cyano-4-methyl biphenyl Toluene Sodium Azide Sol.Recovery Triethylamine Hydrochloride Stage I Evaporation Loss Sulfuric acid Effluent Sodium Nitrate Organic Residue Water

Stage-1 Methylene Dichloride Trityl Chloride Sol.Recovery Triethylamine Stage II Evaporation Loss Methanol Effluent Water Organic Residue

Stage-2 Methylene Dichloride Azobisisobutyronitrile Sol.Recovery N-Bromo Succinimide Stage III Evaporation Loss Ethyl Acetate Effluent Sodium Metabisulfate Organic Residue Water

Diethyl Taratrate N-Bromo Succinimide Azoisobutyronitrile Sol.Recovery Tetrahydrofuran Evaporation Loss Butyraldehyde Stage IV Effluent Ammonium Acetate Organic Residue Acetic acid Process Emissions Sodium Hydroxide Water

Stage-4 Toluene Tetrahydrofuran Sol.Recovery Methyl Magesium Chloride Evaporation Loss Stage V (22%) in Tetrahydrofuran Effluent Hydrochloric acid (35%) Organic Residue Sodium Chloride Water

53 ANNEXURE - II

PRODUCT : Olmesartan Medoxomil

Flow Chart

Stage-3 Stage-5 Acetone Sol.Recovery Sodium Hydroxide Stage VI Evaporation Loss Tetrabutylammonium Bromide Effluent Methanol Organic Residue Water

Stage-6 4-(Chloromethyl)-5-methyl-1,3- dioxol-2-one Sol.Recovery Triethylamine Stage VII Evaporation Loss Dimethylacetimide Effluent Methanol Organic Residue Water

Stage-7 Sol.Recovery Acetic acid Evaporation Loss StageVIII Isopropyl Alcohol Effluent Water Organic Residue

Olmesartan Medoxomil

54 ANNEXURE - II

PRODUCT : Pregabalin

Description :

Stage-1 : Isovalaraldehyde on reaction with Ethyl Cyanoacetate in presence of Di-n-Propylamine, Diethyl malonate and Hydrochloric acid in n-Hexane solvent medium to get Stage-1 Compound.

Stage-2 : Stage-1 Compound is on reaction with Urea in presence of Sodium Hydroxide in Toluene solvent medium to give Stage-2 Intermadiate.

Stage-3 : Stage-2 Intermadiate gets resolution with (R)-(+)-Phenylethylamine in presence of Chloroform and Ethanol solvent media to form Stage-3 Compound.

Stage-4 : Stage-3 Compound is on reaction with Hydrochloric acid in presence of Chloroform solvent medium to give Stage-4 Intermadiate.

Stage-5 : Stage-4 Intermadiate on hydrolysis in presence of Bromine, Sodium Hydroxide and Hydrochloric acid in Isopropyl Alcohol solvent medium to obtain Pregabalin.

55 ANNEXURE - II

PRODUCT : Pregabalin

Flow Chart

Isovalaraldehyde Ethyl Cyanoacetate Sol.Recovery Di-n-Propylamine Evaporation Loss Diethyl malonate Stage I Effluent n-Hexane Organic Residue Hydrochloric acid (35%) Process Emissions Water

Stage-1 Sol.Recovery Urea Evaporation Loss Sodium Hydroxide Stage II Effluent Toluene Organic Residue Water

Stage-2 (R)-(+)-Phenylethylamine Sol.Recovery Stage III Chloroform Evaporation Loss Ethanol Organic Residue

Stage-3 Sol.Recovery Hydrochloric acid (35%) Evaporation Loss Chloroform Stage IV Effluent Sodium Hydroxide Organic Residue Water

Stage-4 Bromine Sol.Recovery Sodium Hydroxide Evaporation Loss Stage V Hydrochloric acid (35%) Effluent Isopropyl Alcohol Organic Residue Water

Pregabalin

56 ANNEXURE - II

PRODUCT : Quetiapine Hemifumarate

Description :

Stage-1 : Benzene thiol is on reaction with 1-Chloro-2-Nitrobenzene in presence of Isopropyl Alcohol solvent medium to form Stage-1 Compound.

Stage-2 : Stage-1 Compound on reduction in presence of Raney Nickel catalyst in Methanol solvent medium to get Stage-2 Intermediate.

Stage-3 : Stage-2 Intermediate on reaction with Phenyl Chloroformate in presence of Potassium Carbonate in Toluene and Methanol solvent media to give Stage-3 Compound.

Stage-4 : Stage-3 Compound in presence of Polyphosphoric acid in Dimethylformamide and Acetone solvent media to form Stage-4 Intermediate.

Stage-5 : 2-(2-Chloroethoxy)ethanol on reaction with Piperizine in presence of Hydrochloric acid and Sodium Hydroxide in aqueous medium to get Stage-5 Compound.

Stage-6 : Stage-4 Intermediate on reaction with Stage-5 Compound in presence of Sodum Hydroxide and Hydrochloric acid in Methylene Dichloride solvent medium to obtain Quitapine Hemifumarate.

57 ANNEXURE - II

PRODUCT : Quetiapine Hemifumarate

Flow Chart

Benzene thiol Sol.Recovery 1-Chloro-2-Nitrobenzene Evaporation Loss Isopropyl Alcohol Stage I Effluent Water Organic Residue Process Emissions

Stage-1 Sol.Recovery Methanol Evaporation Loss Raney Nickel Stage II Effluent Hydrogen Organic Residue Process Emissions

Stage-2 Phenyl Chloroformate Sol.Recovery Toluene Evaporation Loss Stage III Potassium Carbonate Effluent Methanol Organic Residue Water Process Emissions

Stage-3 Polyphosphoric acid Sol.Recovery Dimethylformamide Stage IV Evaporation Loss Acetone Effluent Water Organic Residue

2-(2-Chloroethoxy)ethanol Piperizine Hydrochloric acid ( 35% ) Stage V Effluent Sodium Hydroxide ( 40% ) Water

Stage-4 Stage-5 Sol.Recovery Hydrochloric acid (35%) Evaporation Loss Stage VI Methylene Dichloride Effluent Sodum Hydroxide Organic Residue Water

Quetiapine Hemifumarate

58 ANNEXURE - II

PRODUCT : Raloxifene Hydrochloride

Description :

Stage-1 : 1-(4-Methoxyphenyl)ethanone on reaction with Bromine in presence of Sodium Hydroxide in Methanol solvent medium to form Stage-1 Compound.

Stage-2 : Stage-1 Compound gets reacted with 3-Methoxy Benzenethiol in presence of Potassium Hydroxide in Methanol solvent medium to get Stage-2 Intermediate.

Stage-3 : Stage-2 Intermediate in presence of Polyphosphoric acid and Sodium Sulfate in Acetone and Ethyl Acetate solvent media to give Stage-3 Compound.

Stage-4 : Methylparaben reacts with 2-Chloroethyl Piperidine Hydrochloride in presence of Potassium Carbonate in Acetone and Methanol solvent media to form Stage-4 Intermediate. Stage-5 : Stage-3 Compound on condensation with Stage-4 Intermediate in presence of Phophorous Pentachloride, Sodium Hydroxide, N-Phenylmercapton and Sodium Sulfate in Methylene Dichloride solvent medium to obtain Raloxifene Hydrochloride.

59 ANNEXURE - II

PRODUCT : Raloxifene Hydrochloride

Flow Chart

1-(4-Methoxyphenyl)ethanone Bromine Sol.Recovery Methanol Stage I Evaporation Loss Sodium Hydroxide Effluent Water

Stage-1 3-Methoxy Benzenethiol Sol.Recovery Potassium Hydroxide Stage II Evaporation Loss Methanol Effluent Water Organic Residue

Stage-2 Polyphosphoric acid Sol.Recovery Acetone Evaporation Loss Stage III Ethyl Acetate Effluent Sodium Sulfate Organic Residue Water Inorganic Solid Waste

Methylparaben Acetone Sol.Recovery 2-Chloroethyl Piperidine Evaporation Loss Hydrochloride Stage IV Effluent Potassium Carbonate Organic Residue Methanol Process Emissions Water

Stage-3 Stage-4 Phophorous Pentachloride Sol.Recovery Sodium Hydroxide Evaporation Loss Stage V Methylene Dichloride Effluent N-Phenylmercapton Organic Residue Sodium Sulfate Inorganic Solid Waste Water

Raloxifene Hydrochloride

60 ANNEXURE - II

PRODUCT : Telmisartan

Description :

Stage-1 : Methyl-3-nitro-4-(butanoyl amine)-5-methylbenzoate on reduction with Hydrogen in presence of Methanol solvent medium to form Stage-1 Compound.

Stage-2 : Stage-1 Compound in presence of Acetic acid and Methylene Dichloride solvent media to get Stage-2 Intermediate.

Stage-3 : Stage-2 Intermediate on reaction with Sodium Hydroxide in presence of Methanol solvent medium to give Stage-3 Compound.

Stage-4 : Stage-3 Compound on reaction with N-Methyl-1,2-benzenediamine dihydrochloride in presence of Polyphosphoric acid and Sodium Hydroxide in Toluene and Methanol solvent medium to get Stage-4 Product.

Stage-5 : 2-Cyano-4-methyl byphenyl on reaction with N-Bromo Succinimide in presence of Azoisobutiro nitrile in Methylene Dichloride solvent medium to form Stage-5 Compound.

Stage-6 : Stage-4 Product on reaction with Stage-5 Compound in presence of Potassium Hydroxide in Acetone, Methanol and Monoethylene Glycol solvent media to obtain Telmisartan.

61 ANNEXURE - II

PRODUCT : Telmisartan

Flow Chart

Methyl-3-nitro-4-(butanoyl amine)-5-methylbenzoate Sol.Recovery Palladium Carbon Stage I Evaporation Loss Methanol Effluent Hydrogen Organic Residue

Stage-1 Sol.Recovery Acetic acid Evaporation Loss Stage II Methylene Dichloride Effluent Organic Residue

Stage-2 Sol.Recovery Methanol Stage III Evaporation Loss Sodium Hydroxide Organic Residue

Stage-3 N-Methyl-1,2-benzenediamine Sol.Recovery dihydrochloride Evaporation Loss Toluene Effluent Stage IV Polyphosphoric acid Organic Residue Sodium Hydroxide (47%) Inorgainc Solid Waste Methanol Spent Carbon Carbon

2-Cyano-4-methyl byphenyl Methylene Dichloride Sol.Recovery Azoisobutironitrile Stage V Evaporation Loss N-Bromo Succinimide Effluent Water Organic Residue

Stage-4 Stage-5 Sol.Recovery Potassium Hydroxide Evaporation Loss Acetone Effluent Stage VI Monoethylene Glycol Organic Residue Methanol Spent Carbon Carbon Process Emissions Water

Telmisartan

62 ANNEXURE - II

PRODUCT : Emtricitabine

Description :

Stage-1 : L-Menthol on reaction with Glyoxalic acid in presence of Sodium Bisulfate, Formaldehyde and Sulfuric acid in Cyclohexane solvent medium to get Stage-1 Compound.

Stage-2 : Stage-1 Compound on reaction with 2,5-Dihydroxy-1,4-Dithiane in presence of Acetic acid and Triethylamine in Toluene and Hexane solvent media to give Stage-2 Intermediate.

Stage-3 : Stage-2 Intermediate reacts with 5-Fluorocytosine in presence of Thionyl Chloride, Triethylamine and Hexamethyldisilazane in Methylene Dichloride and Methanol solvent media to form Stage-3 Compound.

Stage-4 : Stage-3 Compound on reduction with Sodium Borohydride in presence of Dipotassium Hydrogen Orthophosphate, Sodium Hydroxide and Hydrochloric acid in Isopropyl Alchol, Toluene and Ethanol solvent media to obtain Emtricitabine.

63 ANNEXURE - II

PRODUCT : Emtricitabine

Flow Chart

L-Menthol Glyoxalic acid Cyclohexane Sol.Recovery Sodium Bisulfate Stage I Evaporation Loss Sulfuric acid Effluent Formaldehyde (40%) Organic Residue Water

Stage-1 Acetic acid Sol.Recovery Toluene Evaporation Loss Stage II Triethylamine Organic Residue 2,5-Dihydroxy-1,4-Dithiane Process Emissions Hexane

Stage-2 Methylene Dichloride Oxalyl Chloride Sol.Recovery 5-Fluorocytosine Evaporation Loss Stage III Hexamethyldisilazane Effluent Methanol Organic Residue Triethylamine Water

Stage-3 Isopropyl Alchol Dipotassium Hydrogen Orthophosphate Sodium Hydroxide Sol.Recovery Sodium Borohydride Evaporation Loss Hydrochloric acid (35%) Stage IV Effluent Toluene Organic Residue Ethanol Spent Carbon Isopropyl Alchol Hydrochloride Process Emissions (20%) Carbon Water

Emtricitabine

64 ANNEXURE - II

PRODUCT : Lamivudine Salicylate

Description :

Stage-1 : L-Menthol on reaction with Glyoxalic acid in presence of Sodium Bisulfate, Formaldehyde and Sulfuric acid in Cyclohexane solvent medium to get Stage-1 Compound.

Stage-2 : Stage-1 Compound on reaction with 2,5-Dihydroxy-1,4-Dithiane in presence of Acetic acid and Triethylamine in Toluene and Hexane solvent media to give Stage-2 Intermediate.

Stage-3 : Stage-2 Intermediate reacts with Cytosine in presence of Thionyl Chloride, Triethylamine and Hexamethyldisilazane in Methylene Dichloride and Toluene, Isopropyl Alochol and Dimethylformamide solvent media to form Stage-3 Compound. Stage-4 : Stage-3 Compound on reduction with Sodium Borohydride in presence of Dipotassium Hydrogen Orthophosphate, Sodium Hydroxide, Salicylic acid and Hydrochloric acid in Isopropyl Alchol, Toluene and Ethanol solvent media to obtain Lamivudine Salicylate.

65 ANNEXURE - II

PRODUCT : Lamivudine Salicylate

Flow Chart

L-Menthol Glyoxalic acid Cyclohexane Sol.Recovery Sodium Bisulfate Stage I Evaporation Loss Sulfuric acid Effluent Formaldehyde (40%) Organic Residue Water

Stage-1 Acetic acid Toluene Sol.Recovery Triethylamine Stage II Evaporation Loss 2,5-Dihydroxy-1,4-Dithiane Organic Residue Hexane Process Emissions

Stage-2 Methylene Dichloride Oxalyl Chloride Cytosine Sol.Recovery Hexamethyldisilazane Evaporation Loss Stage III Toluene Effluent Triethylamine Organic Residue Isopropyl Alochol Dimethylformamide Water

Stage-3 Isopropyl Alchol Dipotassium Hydrogen Orthophosphate Sol.Recovery Sodium Hydroxide Evaporation Loss Sodium Borohydride Effluent Stage IV Hydrochloric acid (35%) Organic Residue Toluene Spent Carbon Ethanol Process Emissions Salicylic acid Carbon Water

Lamivudine Salicylate

66 ANNEXURE - III

67 ANNEXURE - IV

WATER BALANCE

Item Water Waste Water Treatment Method Requirement Generation in KLD in KLD

Forced evaporation and Process 24.4 30.6* the condensate sent to Effluent Treatment Plant for reuse Floor & Reactor 3.0 3.0 washings Boiler & Cooling Full Fledge ETP & 120.0 10.0 treated water reused for Tower Cooling towers / Boilers D.M. Regeneration 1.0 1.0

Scrubber, Q.C & 6.5 2.0 R&D

Sent to Sewage Domestic 10.5 10.0 Treatment plant and treated used for Gardening Total 165.4 56.6

Note: * 30.6 KLD consists of 3458 Kg of inorganics and 987 kg of organics and 29.26 KLD water.

68 ANNEXURE - V

List of Hazardous Chemicals

Raw Material

2-Chloro Benzaldehyde Acetonitrile Ammonia Solution (25%) Benzene Sulfonic acid Benzylamine Diethyl Malonate Dimethylformamide Ethanol Hydrochloric Acid (35%) Methylene Dichloride Monomethyl amine (30%) n-Hexane Phthalic Anhydride Propionaldehyde Pyridine Sodium Hydride (40%) Sulfuric Acid Sulfuryl Chloride Tetrahydrofuran Toluene Triethylamine

69 ANNEXURE - VI

SOLID WASTE GENERATION FORM THE PLANT

Sl. Source TPD* Handling Disposal No. Method 1. Organic residue 1.51 HDPE Drums 2. Inorganic & 3.72 HDPE Bags Evaporation Salt Sent to TSDF

3. Spent Carbon 0.62 HDPE Drums 4. ETP Sludge 0.2 HDPE Bags 5. Boiler Ash 16.0 Stored in Sold to Brick covered area Manufactures Total 22.05

* Solid waste quantities on worst combination (any four products at a time)

70 ANNEXURE - VII

STACK EMISSION DETAILS

Source Stack Diameter Temperature Flue Gas Exit Gas SPM SO2 NOx Height (m) in oK Flow rate Velocity (m) (m3/Hr) in m/sec Kg/hr 10.0 TPH Coal fired 30 0.7 423 21950 15.8 1.38 10.8 5.4 Boiler

71 ANNEXURE -VIII

PROCESS EMISSION DETAILS

HCl, Ammonia, CO2, N2 and H2 emissions are liberated from the process. HCl (25.87 Kg/day) and Ammonia (16.49 Kg/day) will be scrubbed in the scrubber and dilute HCl and Liquid

Ammonia will be used for Neutralisation. N2 (6.85Kg/day) and CO2 (258.99 Kg/day) will be routed to atmosphere through vents and H2 (27.11 Kg/day) will be diffused with flame arrestor. Product wise gaseous emissions and its treatment method details are given below. Name of Sl. the Quantity Product Treatment Method No. Process Kg/day Emission Propose Bulk Drugs – Campaign products (4 products at a time) CO 53.67 Dispersed into atmosphere 1. Sparfloxacin 2 H2 7.5 Diffused with flame arrestor NH3 3.59 Scrubbed with water 2. Mirtazapine H2 0.89 Diffused with flame arrestor 3. Topiramate Nil ------4. Olanzapine Nil ------5. Amlodipine Besylate H2 2.07 Diffused with flame arrestor HCl 12.0 Scrubbed with water Diffused 6. Montelukast Sodium H2 1.0 with flame arrestor Name of Sl. the Quantity Product Treatment Method No. Process Kg/day Emission NH3 7.81 Scrubbed with water CO2 28.05 Dispersed into atmosphere 7. Loratadine N2 6.85 Dispersed into atmosphere HCl 13.87 Scrubbed with water CO2 15.6 Dispersed into atmosphere 8. Valsartan H2 8.57 Diffused with flame arrestor Clopidogrel 9. CO2 58.7 Dispersed into atmosphere Hydrogensulfate 10. Gabapentin CO2 118.57 Dispersed into atmosphere 5-Amino-1-cyclopropyl- 6,7,8-trifluoro-4-oxo- CO2 24.35 Dispersed into atmosphere 11. 1,4-dihydro-quinoline-3- H2 4.17 Diffused with flame arrestor carboxylic acid ethyl ester 2-(4-Methyl-2-phenyl 12. piperazin-1-yl) pyridine- NH3 5.09 Scrubbed with water 3-carboxylic acid 2,3:4,5-Bis-O-(1-Methyl 13. ethylidene)-b- Nil ------Fructopyranose 2-Methyl-4-amino-10H- 14. Nil ------thieno[2,3-b][1,5]

72 ANNEXURE -VIII benzodiazepine Hydrochloride Ethyl-4-[2-(1,3-Dioxo- 1,3-dihydro-2H- 15. H2 1.38 Diffused with flame arrestor isoindol-2-yl)-ethoxy]-3- oxobutanoate (E)-2-(3-{3-[2-(7- Chloro-2-quinolinyl) 16. vinyl] phenyl}-3-oxo Nil ------propyl) benzoic acid methyl ester N-[(2-Cyano-(1,1'- CO2 12.51 Dispersed into atmosphere 17. biphenyl)-4-yl) methyl] H2 6.87 Diffused with flame arrestor valine methyl ester (+)-2-(2-Chlorophenyl)- N-(2-thienyl) ethyl) 18. CO2 27.16 Dispersed into atmosphere glycine methyl ester hydrochloride

ANNEXURE - IX

73 ANNEXURE - IX

74 ANNEXURE - IX

75 ANNEXURE - IX

76 ANNEXURE - IX

77 ANNEXURE - IX

78 ANNEXURE - IX

79 ANNEXURE - X ANNEXURE -I

80 ANNEXURE - XI

81 ANNEXURE - XI

82 ANNEXURE - XI

83 ANNEXURE - XI

84 ANNEXURE - XI

85 ANNEXURE - XI

86 ANNEXURE - XI

87 ANNEXURE - XI

88 ANNEXURE - XI

89 ANNEXURE - XI

90 ANNEXURE - XII

91 ANNEXURE - XII

92 ANNEXURE - XII

93 ANNEXURE - XII

94 ANNEXURE - XII

95 ANNEXURE - XII

96 ANNEXURE - XII

97 ANNEXURE - XII