LIST OF ANNEXURES

SR. NO. NAME OF ANNEXURE I List of Products and Raw materials along with their Production Capacity II Layout Map of the Plant III Brief Manufacturing Process Description IV Details of water consumption & waste water generation V Details of Effluent Treatment Scheme VI Details of Hazardous Waste Generation and Disposal VII Details of Stacks and Vents, Fuel & Energy Requirements VIII Details of Hazardous Chemicals Storage & Handling IX Socio-economic Impacts X Proposed Terms of Reference XI GIDC Plot Allotment Letter XII ETL Membership Letter (M/s. ETL) XIII TSDF & CHWIF Membership Letter (M/s BEIL) XIV Toposheet XV Copy of existing CCA

ANNEXURE-I ______LIST OF PRODUCTS ALONG WITH THEIR PRODUCTION CAPACITY WITH RAW MATERIALS

PRODUCTION CAPACITY (MT/MONTH) SR. PRODUCTS CAS NO NO EXISTING ADDITIONAL TOTAL QUANTITY QUANTITY PROPOSED QUANTITY EXISITING PRODUCTS

1 Optical Brightening Agent 13001-39-3 1.0 0 1.0

2 Ortho Toluene Nitrite 88-72-2 4.0 0 4.0

TOTAL (EXISITING PRODUCTS) 5.0 0 5.0

PROPOSED PRODUCTS

1 Darunavir 206361-99-1 5 5

2 Levosulpiride 23672-07-3 10 10

3 Montelukast Sodium 151767-02-1 5.5 5.5

4 Tramadol hydrochloride 36282-47-0 7 7 5 Nifedipine 21829-25-4 4.5 4.5

6 Quetiapinehemifumarate 111974-72-2 3 3

7 Furosemide 54-31-9 3.5 3.5 8 Risedronate Sodium 105462-24-6 4.5 4.5

66108-95-

0/60166-93- 9 Iohexol/Iopamidol/Iodixanol 0/92339-11-

2 6 6 10 Lauryl Pyridinium chloride 104-74-5 10 10 11 Vildagliptin 274901-16-5 4 4 12 Ambroxol Hydrochloride 23828-92-4 4 4

13 Pantaprazole Sodium 138786-67-1 7.5 7.5

14 Miconazole Nitrate 22916-47-8 0 4.5 4.5 15 Dorzolamide Hcl 130693-82-2 4 4 16 Bosentan 147536-97-8 5.5 5.5 17 Febuxostat 144060-53-7 10 10 18 Fesoterodine NDMF 286930-02-7 6 6 19 Rizatriptan 145202-66-0 2.5 2.5 20 Olanzapine 132539-06-1 4.5 4.5 21 Levocetirizine 130016-77-8 5 5 22 Revaroxaban 366789-02-8 7 7 23 Ciprofloxacin 85721-33-1 10 10 24 Agomelatine 138112-76-2 10 10 25 Brinzolamide 138890-62-7 2.5 2.5 26 Atorvastatin Calcium 134523-00-5 8.3 8.3 27 Capecitabine 154361-50-9 3.5 3.5 28 Diacerein 13739-02-1 3.5 3.5 29 Dabitgatran 211915-06-9 3 3 30 Vilazodone Hydrochloride 163521-08-2 2 2 31 Posaconazole 171228-49-2 5.5 5.5 32 Dapoxetine Hydrochloride 129938-20-1 3.5 3.5 33 Canagliflozin 842133-18-0 2.5 2.5 34 Bronopol(BP) 52-51-7 7 7 35 Carbamazepine 298-46-4 5.5 5.5 36 Cefsulodine Sodium 52152-93-9 6.5 6.5 37 Cilinidipine 132203-70-4 3.5 3.5 38 Nebivolol 99200-09-6 39 Nebivolol HCL 152520-56-4 0.5 0.5

40 Donepezil Hydrochloride 120011-70-3 41 Brimonidine Tartrate 70359-46-5

42 Captopril 62571-86-2 43 Cilostazol 73963-72-1 44 Clopidogrel bisulphate 120202-66-6 45 Entacapone 130929-57-6

46 Graniserton HCL 107007-99-8 10 10 47 Meloxicam 71125-38-7 48 Modafinil 68693-11-8 49 Piogltazone HCL 112529-15-4 50 Zaltoprofen 74711-43-6 51 Zonisamide 68291-97-4 52 Pregabalin 148553-50-8 53 Rampril 87333-19-5 54 Sodium Valroate 1069-66-5 TOTAL(Proposed) 0 210.8 210.8 TOTAL (EXISTING+PROPOSED) 5.0 210.8 215.8 RAW MATERIAL CONSUMPTION: EXISITNG PRODUCTS SR. Raw Materials Quantity Name of Products NO. (KG/KG) [1] Ortho toluene nitrile 2.66 Optical Brightening Agent Chlorine gas 4.00 Trimethyl phosphate 1.78 OCBC 1.33

Orthoxylene 1.11

Terpthaldehyde ester 0.45 Sodium methoxide 1.60 Dimethyl formamide 2.22 [2] OTA 2.33 Sulphuric acid 0.83 Ortho toluene Nitrite Urea 1.67 Soda ash 0.50 Caustic lye 1.00

PROPOSED PRODUCTS

Sr. Quantity Name of Product Raw Materials No. (KG/KG)

[1] Darunavir (3aS,4S,6aR) -4-METHOXY terahydrofuro -[ 0. 628 Hydrochloric Acid 0. 145 Sodium Borohydride 0. 87 0 Hydrogen 0.00 7 Ethyl Acetate 2.300 Tetrahydrofuran 5.020 Sodium Hydroxide 0. 13 0 isobutyl benzenesulfonamide 1.430 Disucinimidyl carbonate 0. 963 Sulphuric acid 0. 10 0 2-Methyl2 -Butanol 0. 60 0 Methylene Chloride 3.000 Cyclohexane 2.400 Sodium bicarbonate 0.0 20 Sodium chloride 0.0 10 Sodium sulphate 0.0 10 Sodium hydroxide 0.00 8 Activated carbon 0.0 20 [2] Levosulpiride Monoethylene Glyco 1.000 2-Methoxy-5-Sulphomyl Benzoate 0.750 S-1-Ethyl 5 - Amino methyl Pyrolidine 0. 390 [3] Motelukast Sodium 2-[2-[3(s)-[3-[2-(7-chloro-2-quinoliny1) -Ethanl ]pheny1]-3-hydroxypropy1]pheny1-2 propanol 1.326 2-[1-(Sunfonyl methy1) Cyclopropy1]acetic acid 0.423 Methane sulfonyl chloride 0.332 Sodium hydroxide 0.182 N,N-Diisopropylethylamine 0.007 Hydrochloric acid 0.046 Sodium chloride 0.007 Acetic acid 0.013 Toluene 1.000 Acetonitrile 0.867 Methanol 1.333 n Hexane 1.733 Activated Carbon 0.013 [4] Tramadol Hydrochloride Isopropyl Alcohol 2.069 Cyclohexanone 0. 345 Para Formaldehyde 0. 103 Dimethyl amine Hcl 0. 281 Caustic Lye 0. 414 Tetrahydrofuran 1.034 Manganese Turning 0.0 86 Catalyst 0.00 3 M bromo Anisole 0.0 69 Hcl 0. 345 Toluene 2.758 Methanol 1.724 Nitric Acid 0. 217 IPA Hcl 0. 638 [5] Nifedipine Methyl Aceto Acetate 2.250 Methanol 13 .700 ONBA 1.500 Acetic Acid 3.200 Liquid Ammonia 1.100 [6] Quetiapine hemifumarate Dibenzo - (1,4) - thiazepine - 11 (10H) one 3 - 2.780 Fumaric acid 0. 402 Thionyl chloride 0.0 50 Hydrochloric acid 0.0 23 Sodium hydroxide 0.0 25 Sodium Carbonate 0. 300 Toluene 7.000 8.500 Activated Carbon 0.0 50 [7] Furosemide Lasamide 1.300 Furfuryl amine 2.100 Iso propyl Alcohol 4.850 Caustic soda 0.600 Citric acid 0.100 EDTA 0.010 Hydrose 0.010 Hyflow 0.150 Acetic Acid 0.500 [8] Risedronate Sodium 3-Pyridyl Acetic Acid 2.446 Diethyl carbonate 0.750 Caustic soda lye 0.050 Phosphorous trichloride 0.025 Methane sulphonic Acid 0.500 Isopropyl alcohol 5.800 Sodium hydroxide flakes 0.309 Hyflow 0.050 Activated carbon 0.050 Hydrochloric acid 0.220 [9] L-Acetoxy propionyl chloride 1.200 Iohexol/Iopamidol/Iodixano 5- amino-2, 4, 6- Tri iodoisophthaloyl di 1.500 l chloride 2-Amino-1, 3-propanediol 1.200 Sodium Hydroxide 0.350 Isopropyl Alcohol 4.000 [10] Lauryl Pyridinium Chloride Lauryl chloride 0.722 Pyridine 0.560 Methyl Ethyl ketone 4.000 Acetone 2.000 [11] Vildagliptin KSM I 0.770 KSM II 0.720 DMF 5.400 Methylene dichloride 15.000 Potassium Carbonate 2.600 Isopropyl Acetate 5.040 Sulphate 3.750 Sodium chloride 0. 630 Acetone 12.500 Charcoal 0.050 [12] Ambroxol Hydrochloride Ambroxol Base 0.912 Isopropyl Alcohol 10.500 Activated Carbon 0.015 [13] Pantaprazole Sodium 2-Chloromethyl-3-4-dimethox pyridine 0.770 hydrochloride 5-difluoromethoxy-2-mercapto benzimidazole 0.740 Sodium Hydroxide 0.410 Isopropyl Alcohol 11.530 Sodium Hypochlorite (10%aqueous) 2.790 Acetone 6.230 [14] Miconazole Nitrate TCAP 1.059 Imidazol 0.424 Sodium Carbonate 0.848 Toluene 9.481 Sodium borohydride 0.069 TBAB 0.375 Caustic Soda flake 3.750 DCBC 0.917 Hydrose 0.010 Carbon 0.350 Nitric acid 0.300 Methanol 2.300 [15] Dorzolamide Hcl (+-)- Trans -5,6 - DIHYDRO-4H-4-Ethyl amino- 2.990 6-methyltheino[2,3- N butanol 23.200 Methanol 30.200 Ethyl Acetate 14.500

Acetone 0.800 Activated carbon 0.300 Sodium Bicarbonate 1.500 Sodium Chloride 1.500 Sodium Hydroxide 0.258 Hydrochloric acid 0.336 [16] Bosentan 4,6 Dichloro 5 (2-Methoxyphenoxy)2,2 0.726 Bipsimidine 4 Tert Butylbenzene Sulfonamide 0.443 Hydrochloric Acid 0.179 Potassium Carbonate 1.206 Sodium Tert Butoxide 0.998 Ethylene Glycol 12.339 [17] Febuxostat KSM 1.547 Isobutyl Bromide 1.162 Potassium Carbonate 1.834 Ammonium Hydroxide Hcl 0.323 Sodium Carbonate 0.314 Sodium Hydroxide 0.297 Hydrochloric Acid 0.289 Acetone 0.750 [18] Fesoterodine NDMF Benzyl Amine DPTT 5.454 Sodium Carbonate 5.726 Ceric Ammonium nitrate 12.544 Barium Borohydrate (BaBH4) 0.774 Fumaric Acid 1.477 Hydrogen gas 0.013 Isobutyl Chloride 0.340 Triethylamine 0.301 [19] Rizatriptan Triazole Compound 1.250 Dimethyl amine Indole 2.000 Catalyst 1.120 Acetonitrile 5.000 Methanol 6.250 [20] Olanzapine Methyl Piperazinyl 1.060 Chloro-thiano benzodiazepine 0.933

N N DMA 5.330

Catalyst 0.130

Acetonitrile 4.000

[21] Levocetirizine 1-[4Chlorophenyl) Phenyl methyl] piperizine 1.820 L-Tartaric acid 2-Chloroethoxy 0.620 Acetonitrile 1.450 Sodium Carbonate 0.350 Potassium Iodide 0.150 N-Butanol 2.250 Hydrochloric Acid 0.320 Ethyl Acetate 2.950 [22] Rivaroxaban (4-4-Aminophenyl)-morpholin-3-one 1.410 Glycidyl Phthalimide 1.640 4-Dimethylaminoopyridine (DMAP) 0.010 Carbonyldiimidazole 4.030 5-Chlorothiophene-2-cacoxylic acid 1.230 Sodium Acetate 1.480 Oxalyl Chloride 1.500 Methyl Amine(Aqueous) 1.630 Hydrochloric Acid 0.680 Acetic Acid 0.040 [23] Ciprofloxacin Flouro Quinolic acid 1.000 Piperazine 0.400 Dimethyl Sulphoxide 0.050 Causitc lye 0.950 Hydrochloric Acid 0.600 Methanol 1.400 [24] Agomelatine 2-(7-methoxy-1-napthyl-napthyl) Acetonitrile 1.000 Hydrogen Gas 0.020 Isopropyl Alcohol 0.740 Sodium Acetate (Anhydrous) 0.420 Acetic Acid (Anhydrous) 0.510 [25] Brinzolamide 4(S)-4-hydroxy-6- sulfonamide dioxide 2.610 Methanol sulfonic anhydride 0.600 Ethyl amine 0.330

Ammonia liquor 0.200

Hydrochloric Acid 0.101 Sodium Hydroxide 0.110 Pyridine 0.200 Tetrahydrofuran 10.050 Isopropyl Alcohol 10.950 Sodium Bicarbonate 0.101

Activated Carbon 0.101

Hyflow 0.101 [26] Atorvastatin calcium 1, 1--dimethyl ethyl-6-(2- aminoethyl) 0.770 4- Fluoro-2-methyl-1-oxopropyl 1.176 Cyclohexane 3.000

Isopropyl Alcohol 2.501

Hydrochloric Acid 0.070 Acetonitrile 3.500 Sodium Hydroxide 0.146 Calcium Acetate 0.179 Hyflow 0.012 [27] Capectabine 2,3 di-o-actyl-5-dexy-5-fluorocytidine 1.247 n-Pentyl Chloroformate 0.570 Sodium Hydroxide 0.415 Sodium Bicarbonate 0.050 Hydrochloric Acid 0.075 Methylene Chloride(MDC) 4.000 Methanol 2.500 Ethyl Acetate 5.500 Activated Carbon 0.050 [28] Diacerein Aloe emodine 1.966 Sodium dichromate dihydro 2.168 Sulphuric Acid 0.814 Sodium Hydroxide 0.122 Tetrahydrofuran 22.000 Acetone 6.200 Acetic Anhydride 1.018 N Methyl pyrolidone 3.498 Methanol 2.200 Activated Carbon 0.200 Celite 0.200 [29] Dabigatran 3-[(1-Methyl-2-{[4-(5-oxo-4,5-dihydro-[1,2,4] 0.970 oxadiazol-3-yl)-phenylamino]-methyl)-1H- benzoimidazole-5-carbonyl)-pyridin-2-yl amino]-propionic acidethyl ester Para toluene sulphonic acid 0.250 Acetic acid 0.200 Ethanol 25.000 Hexa Chlorofomate 0.280 Acetone 12.000 Potassium Hydroxide 0.096 Hydrochloric acid 0.004 [30] Vilazodone Hydrochloride 5-{4-(5-Cyano-1H-indol-3-yl)-butyl]-piperazin- 1-yl}-benzofuran-2carboxylicacid methyl ester 1.510 Ammonia 0.951

Methanol 16.100 Hydrochloric acid 0.110 Sodium Hydroxide 30% 0.122 Isopropyl Alcohol 12.000 Activated Carbon 0.200 [31] Posaconazole 2-[2-[3(S)-[3-[2-(7-Chloro-2- Quinolinyl) ethenyl ]pheny]-3 hydroxy propyl] phenyl-2- 1.326 Propanol 2-[1-(sulfonyl methyl) cyclopropyl} acetic acid 0.423 Methane sulfonyl chloride 0.332 sodium hydroxide 0.182

N,N-Disopropyletylamine 0.007

Hydrochloric acid 0.046 Sodium chloride 0.007 Acetic acid 0.013 Toluene 1.000 Acetonitrile 0.867 Methanol 1.333 n-Hexane 1.733 Activated carbon 0.013 [32] Dapoxetine Hydrochloride ᵦ- (dimethylamino) benzenepropanol 1.062 1-fluoronaphthalene 0.865 sodium hydroxide 0.357 Hydrochloric acid Di methyl Sulphoxide (DMSO) 12.5000. 325 n-Propanol 10.000 Activated Carbon 0.250 [33] Canagliflozin 2-(5-bromo-2-methylbenzil)-5-(4- 2.123 flurophenyl)thiophene silyl D-gloconolactone 2.770 Methanol 16.667 Acetone 25.000 Potassium Carbonate 0.333 [34] Bronopol(BP) Nitro Methane 0.333 Methanol 1.667 caustic 0.233 Formaldehyde 0.733 Carbon 0.017 Bromine 0.883 [35] Carbamazepine Methanol 1.014 Imino stilbene carbonyl Chloride 1.282 Ammonia Liquor 2.802

Acetone 6.504

Toluene 0.040 Caustic lye 0.406 Hyflow 0.013 Activated Carbon 0.012 [36] Cefsulodine Sodium RS-a-Sulfophenyl acetic acid 0.515 (S)-a-Methyl benzyl amine 0.288 Acetonitrile 6.150 1-Hydroxy benzotriazole 0.309

Methane sulphonyl chloride 0.261

Sodium bicarbonate 0.100 Methylene dichloride 5.125 Hexane 3.000 Sodium hydroxide 0,086 7-Amino cephalosporic acid 0.598 Boron triflouride etherate 1.875 Tert-butyl acetate 0.255 Hyflow 0.050

Zinc chloride 0.025

Triethyl amine 0.025

Ethyl acetate 1.025 Di isopropyl ether 0.500 Pyridine -4-carboxamide 0.242 Sodium Iodide 0.200 Dimethyl formamine 0.276 Hydrochloric Acid 0.025

Ethanol 1.750

Sodium hydroxide 0.027

DMF 1.500 Diethyl ether 2.250 [37] Cilinidipine Methanol 7.500 2 Methoxy Ethyl Acetoacetate 3.250 Cinramyl Aceto Acetate 1.000

3 Nitro Benzaldehyde 0.750

Ammonium Carbonate 1.000 [38] NEBIVOLOL Benzopyran-2- Carboxaldehyde Deri 1.4 Trimethyl sulfoxonium Iodide 1.15 Potassium hydroxide 0.56 Benzylamine 0.4 Toluene 3.0 Ammonium formate 0.6 (Hydrogen source) Pd/C 0.01 Methanol 5.2 [39] NEBIVOLOL HCL NSR-19C 1.0 Methanol 7.6 Acetonitrile 3.0 Diisopropyl ether 6.0 HCl (CP) 0.6 Methanol 144.1 NSR-19D 0.3 IPA HCl (20%) 3.4 Hyflow 1.7 [40] DONEPEZIL NSR-10A HYDROCHLORIDE 1.61

NSR-10B 1.39 Sodium methoxide solution (30%) 1.57 Methanol 42.33 Hydrochloric acid 0.44 NSR-10C 0.78 Recycled NSR-10C from Donepezil 0.06 HydrochlorideRecycled NSR-10C crude from (cycle Donepezil-1) 0.12 HydrochlorideHydrochloric acid crude (cycle -2) 2.00 Ammonia solution 16.39 Ethyl acetate 60.00 Hydrogen gas 1.11 Hyflo super cel 1.11 Methanol 147.22 Methanol 16.39 Methyl tertiary butyl ether 23.99 Activated charcoal 0.11 Hyflo super cel 0.28 Donepezil Hydrochloride seed 0.02 [41] BRIMONIDINE TARTRATE NSR-2A 5 Benzoyl chloride 3.8 NSR-2B 2.1 Acetone 15 Sodium Hydroxide Flakes 4.5 Hydrochloric acid 10 Hyflo supercel 5.1 Ethylenediamine 2.05 Chlorobenzene 55.5 Isopropyl alcohol 15 Hydrochloric acid 2 Sodium Hydroxide flakes 7.1 Ethylacetate 72 Hyflo supercel 138.6 [42] CAPTOPRIL NSR-5A 3.55 NSR-5B 4.36 Thionyl chloride 5.91 Methanol 1.82 Sodium hydroxide lye 22.73 NSR-5C 1.82 Methylene chloride 9.09 N,N-Dimethyl aniline 1.91 Hydrochloric acid 1.82 Ammonia solution 1.18 Hydrochloric acid 2.05 NSR-5D 0.28 Activated charcoal 0.03 Hyflo super cel 0.03 Sodium chloride 2.59 Ethyl acetate 14.77 [43] CILOSTAZOL NSR-7A 0.92 NSR-7B 0.70 Sodiumhydroxide 0.44 Sodiumsulphate 0.71 NSR-7C 0.03 Activated charcoal 0.01 Toluene 0.64 Methanol 3.21 Methanol 26.38 Activated carbon 0.09 hyflow 0.09 [44] CLOPIDOGREL BISULPHATE NSR-8A 5.43 Sodium bicarbonate 1.74 Sulphuric acid 0.83 Methanol 18.26 13.04 Mehtyl-Alpha-bromo-2-hlorophenyl acetate 5.00 Sodium bicarbonate 3.91 NSR-8B 3.22 Acetone 29.57 Chloroform 17.39 Methanol 28.26 NSR-8C 2.43 Clopidogrel seed-1 0.06 Sodium bicarbonate 1.83 Chloroform 22.17 Ethyl acetate 19.13 Activated charcoal 0.09 Hyflo super cel 0.17 Sulphuric acid 0.52 Clopidogrel seed-2 0.02 Sodium bicarbonate 2.74 Chloroform 22.17 Ethyl acetate 23.48 Activated charcoal 0.09 Hyflo super cel 0.17 Sulphuric acid 0.30 Clopidogrel seed-2 0.01 [45] ENTACAPONE NSR-11A 1.79 Nitric acid 1.60 Sulphuric acid 2.07 Methylenedichloride 12.50 5-Nitro Vanillin 1.19 NSR-11B 1.10 Pyridine 2.14 Methylenedichloride 8.93 Hydrochloric acid 7.62 DHNB 0.54 NSR-11C 0.60 NSR-11D 0.65 Isopropyl alcohol 6.65 Acetic acid 2.48 Methanol 1.07 Cyanoacetic acid 0.86 Diethylamine 0.81 NSR-11E 2.02 Tetrahydrofuran 5.60 Methylenedichloride 3.33 Acetic acid 0.29 [46] GRANISERTON HCL NSR-13A 1.13 Thionyl chloride 1.47 NSR-13B 0.03 n-Hexane 16.67 Stage-I 1.00 NSR-13C 0.92 Triethylamine 0.92 Methylenedichloride 35.00 Isopropyl alcohol 21.67 Sodiumbicarbonate 1.33 Hydrochloric acid 0.58 Activated carbon 0.02 E 13.00 [47] MELOXICAM NSR-16A 1.08 NSR-16B 0.47 Meloxicam Crude 1.13 Sodium Hydroxide 0.15 Acetic acid 0.76 Methanol 1.95 Activated Carbon 0.12 Hyflow 0.25 Meloxicam Purified 1.07 Acetic acid 2.96 Meloxicam Purified 1.03 Toluene 4.90 Dimethylformamide 0.49 [48] MODAFINIL NSR-17A 1.21 Ethylene Dichloride 12.12 Triethyl Amine 0.73 Ethyl Chloroformate 0.80 NSR-17B 0.12 Methanolic Ammonia (20%) 16.36 Methanol 6.36 Modafinil Crude 1.03 Methanol 13.33 Activated Carbon 0.06 Hyflow 0.03 [49] PIOGLTAZONE HCL NSR-22A 1.23 Methane sulphonylchloride 1.07 Toluene 13.09 NSR-22B 1.06 Isopropyl alcohol 6.85 Sodium hydroxide 0.41 Methanol 18.52 NSR-22C 0.31 2,4-Thiazolidinone 0.87 Triethylamine 1.01 Potassium Carbonate 1.43 NSR-22D 0.12 NSR-22E 0.10 Dimethylformamide 17.78 Sodiumborohydride 0.31 Hydrochloric acid 1.65 Methanol 8.32 Hydrochloric acid 0.76 Activated charcoal 0.06 Hyflow 0.12 [50] ZALTOPROFEN NSR-27A 1.43 NSR-27B 5.71 Ethylene Dichloride 2.14 Acetone 4.29 Activated carbon 0.05 Hyflow 0.04 NSR-27C 5.36 Sodium carbonate 0.23 Denatured Spirit 2.79 NSR-27D 0.01 Acetic acid 0.82 [51] ZONISAMIDE NSR-28A 2.5 NSR-28B 3.8 NSR-28C 4.4 Methanol 25.0 Ammonia Solution 6.3 Hydrochloric Acid 7.5 Ethyl Acetate 6.3 Ethylene Dichloride 12.3 NSR-28D 2.2 1,4 Dioxane 1.6 Phosphorus Oxy chloride 8.2 Toluene 61.3 Ethyl Acetate 102.1 Activated Carbon 2.1 Hyflow Super cell 0.8 Sodium Chloride 4.4 Anhydrous ammonia 0.8 Acetone 8.3 Activated carbon 1.7 Hyflow supercel 0.4 [52] PREGABALIN 3-isobutylglutaric acid 2.2 acetic anhydride 1.2 Toluene 6.6 4-Dimethyl aminopyridine 0.01 (S)-(-)-phenyl ethylamine 2.84 caustic lye 2 Hydrochloric acid 2.92 Acetone 12.5 Triethylamine 1.09 Ethylchloroformate 1.03 Sodium Azide 1.4 Toluene 13 Methanol 0.5 70% sulphuric acid 24.8 Sodium Hydroxide lye 13 Iso Butanol 8.68 A. carbon 0.02 Hyflow 0.06 [53] RAMIPRIL ECPPA 0.88 Azabicyclo Benzylester 8.33 TEA 0.6 HOBT 0.5 DCC 0.67 MDC 16.67 Sodium Bicarbonate 1.67 Benzyl Ramipril 1.56 Ab. Alcohol 12.5 pd/C 0.16 Hyflow 0.1 Acetonitrile 7.8 [54] SODIUM VALROATE valporic acid 0.91 Acetonitrile 3.5 sodium Hydroxide 0.29 Activated carbon 0.005 hyflow 0.02

ANNEXURE-II

______LAYOUT OF MAP OF THE PLANT

ANNEXURE-III MANUFACTURING PROCESS, CHEMICAL REACTION & MASS BALANCE: Existing [1] Optical brightening Agent

MANUFACTURING PROCESS

Required Qty. of OTN is taken into flask. Chlorine gas is passed through very slowly within 45 to 60hrs. (10 kegs. Gas is passed through within 45 to 60 hrs.) 50% chlorination is carried out. Un-reacted OTN is distilled out under vacuum.Now charge Tri-Methyl Phosphite & Ortho xylene to the flask containing OCBC. Heat it to 100 to110 degree C. Maintain for 30 to 40 hrs. Cool down to room temp. Add Di-methyle formaldehyde and terphaldehyde. Heat it to 700 degree C and start addition of sodium Methoxide within 20 hrs. Cool the batch to 8 to 10 degreeC and recover the solvent added which will be used in the next batch. The sludge is collected nto MS drums. PROCESS FLOW DAIGRAM:

[2]Ortho Toluene Nitrite MANUFACTURING PROCESS Charge Ortho Toluic Acid in reaction vessel under stirring. Add Sulphuric Acid & urea and heat it till reaction is completed. Allow to cool by outside cooling (Jacketed vessel) Add caustic lye or soda ash and neutralize, adjust pH 7.0 – 8.0 & distillate out product. Distillate is finished product and residue store in drums with lid. PROCESS FLOW DAIGRAM:

PROPOSED [1] DARUNAVIR MANUFACTURING PROCESS:

Stage 1 (3aS, 4S, 6aR)-4-methoxy-terahydrofuro -[3,4-b]furan-2-(3H)one is reacted with Sodium boro hydride(NaBH4) and Hydrochloric acid in presence of tetrahydrofuran to give (3R,3aS,6aR) - Hexahydrofuro [2,3-b]furan-3-ol. Reaction is carried out in a reactor with hydrogen,ethyl acetate, tetrahydrofuran and sodium hydroxide as raw materials with water. Stage 2: 4-Amino-N-(2R, 3S)-(3-amino -2-hydroxy-4-phenyl-butyl)-N-isobutyl-benzenesulfonamide is condensed with (3R, 3aS, 4aR) -hexahydrofuro [2, 3-b] furan-3-ol in the presence of disucinimidyl carbonate to yield Darunavir . Reaction is carried out in a reactor using sulphuric acid, 2-Methyl2-Butanol,methylene di chloride, cyclohexane, sodium bicarbonate, sodium chloride, sodium sulphate as raw materials with water. Cyclohexane, methylene dichloride, ethyl acetate, tetrahydrofuran are recovered

CHEMICAL REACTION:

MATERIAL BALANCE:

Input material Quantity Output material Quantity (KG) (KG) (3aS,4S,6aR)-4-METHOXY terahydrofuro-[ Darunavir 628 1000 3,4-b]furan-2-(3h)one

Hydrochloric Acid Recovered 145 4570 Tetrahydrofuran Sodium Borohydride 87 Recovered Ethyl Acetate 2136 Hydrogen Recovered Methylene 7 2775 dichloride Ethyl Acetate 2300 Recovered cyclohexane 2232 Tetrahydrofuran 5020 Spent carbon 20 Sodium Hydroxide Material recovered for 13 1055 second crop isobutyl benzenesulfonamide 1430 Solvent vapor loss 98 Disucinimidyl carbonate 963 Organic residue 1792 Sulphuric acid 10 Effluent to ETP 4353 2-Methyl2-Butanol 60 Methylene Dichloride 3000 Cyclohexane 2400 Sodium bicarbonate 20 Sodium chloride 10 Sodium sulphate 10 Sodium hydroxide 8 Activated carbon 20 Water 3900 Total 20031 Total 20031

[2] LEVOSULPIRIDE

MANUFACTURING PROCESS Charge Mono ethylene glycol in a reactor, start stirring and charge slowly 2-methoxy -5 sulphomyl methyl benzoate powder .Add slowly and gradually liquid(S -) 1 –ethyl -2- aminomethylpyrolindine within 15 -20 min. Start heating and maintain at 60 -70 °C for 8 hrs. Cool it up to 35 °C centri fuge it, mother liquor is reused for next batch. Final reaction mass is dried, pulverized and packed as Levosulpiride. Reaction is carried out in a reactor.Process involves reaction heating and cooling, centrifuging, drying and pulverizing. Monoethylene gl ycol ML is recovered and reused.

CHEMICAL REACTIONS

MATERIAL BALANCE

Input Material Quantity (kg) Output Material Quantity(kg) Monoethylene Glycol 1000 Levosulpiride 1000

2-Methoxy-5- 750 Evaporation losses 160 Sulphomyl Benzoate S-1-Ethyl 5- Amino 390 Mother ethylene 980 methyl Pyrolidine glycol mother liquor Total 2140 Total 2140

[3] Montelukast Sodium

MANUFACTURING PROCESS

2-[2-3(S)-[3-[2-(7 – chloro – 2 – quinolinyl) – ethyl] phenyl]-3-hydroxy propyl] phenyl -2- propanol is condensed with 2 -[1-(sulfonyl methyl) cyclopropyl] acetic acid in presence of Toluene, Acetonitrile and reacted with Sodium hydroxide in presence of metha nol to give Montelukast Sodium . like Acetonitrile,toluene and n Hexane are recovered and reused. Sodium hydroxide. Hydrochloric acid, Sodium chloride Acetic acid ,, Acetonitrile, Methanol,n Hexane,carbon and water are used as main raw materials in a reactor along with Water. Process involves mainly condensation.

CHEMICAL REACTIONS

MATERIAL BALANCE

Input material Quantity Output material Quantity (KG) (KG) 2-[2-[3(s)-[3-[2-(7-chloro- 2-quinoliny1) - Ethanl ]pheny1]-3- hydroxypropy1]pheny1-2 propanol 1326 Montelukast Sodium 1000 2-[1-(Sunfonyl methy1) Cyclopropy1]acetic acid 423 Effluent to ETP 1835 Methane sulphonic acid Methane sulfonyl chloride 332 (byproduct) 158 Sodium hydroxide 182 Recovered Acetonitrile 789 N,N-Diisopropylethylamine 007 Recovered Toluene 910 Hydrochloric acid 046 Recovered n Hexane 1560 Sodium chloride 007 Recovered Methanol 1240 Acetic acid 013 Organic residue 1293 Toluene 1000 Solvent vapor losses 30 Acetonitrile 867 Methanol 1333 n Hexane 1733 Activated Carbon 13 Water 1533 Total 8815 Total 8815

[4] Tramadol Hydrochloride

MANUFACTURING PROCESS

Stage 1 Isopropyl alcohol, cyclohexanone, Pafaformaldehyde and Dimethyl amine are charged in a reactor and slowly heated to reflux and maintain in 89-90 degree C for 10hr and IPA is distilled under vacuum and water is added with making alkaline mass by using Sodium hydroxide lye.The mass is dehydrated under vacuum and cooled.

Stage- 2 Charge THF, Mg turning, catalyst in reactor and heat to reflux and add m-bromo anisole, maintain1 hr and add hydrochloric acid to acidify and extract in toluene. Distilled out Toluene and residue used in next stage and distilled toluene used in next batch.

Stage-3 Methanol and stage-2 product charge in reactor and add Nitric Acid to acidify at 20-30 degree C and stir 2 hr. and centrifuge and dry to obtain powder pack in drum and filtrate liquor distilled and used in next batch.

Stage-4 Toluene, water and stage-3 product charge in reactor and add caustic lye to basify at 20-30 degree C and stir 1 hr. and separate organic layer and distilled and add IPA. HCL is used to acidify and centrifuge and dry to obtain powder, pack in drum and filtrate liquor distilled and used in next batch. Process involves reactions in a reactor, layer separation, distillation, centrifuging and drying. Solvents are recovered and reused.

CHEMICAL REACTIONS

MATERIAL BALANCE:

Input material Quantity Output material Quantity (KG) (KG) Isopropyl Alcohol 2069 Tramadol Hydrochloride 1000 Cyclohexanone 345 Recovered Toluene 2483 Para Formaldehyde Recovered Isopropyl 103 1845 Alcohol Dimethyl amine Hcl 281 Recovered methanol 1552 Caustic Lye 414 Organic residue 262 Tetrahydrofuran 1034 Solvent Vapor losses 109

Manganese Turning 86 Effluent to ETP(Including 4042 Aqueous layer) Catalyst 3 M bromo Anisole 69 Hcl 345 Toluene 2758 Methanol 1724 Nitric Acid 217 IPA Hcl 638 Water 1207 Total 11293 Total 11293

[5] NIFEDIPINE

MANUFACTURING PROCESS

In order to prepare Nifedipine first Methyl 3 amino crotonate(MAC) is produced in MAC reaction vessel. The other raw material required for Nifedipine is benzene Derivative(BD). The BD and MAC are reacted in a Nifedipine reaction vessel.Filtered in centrifuge after crystallization and subsequently these crystals are dried.Process involves reaction,filteration,crystallization and drying.Methanol and acetic acid are recovered and reused.

CHEMICAL REACTIONS

- O + O N O CH3 H3C O + OO

ONBA Methyl Aceto Acetate

[C H O ] [C 7H5NO 3] 5 8 3 Mol.Wt.: 151.12 Mol.Wt : 116.11

- O + O N O

CH3 O

O CH3

BenZylidine Derivative [C H NO ] 12 11 5 Mol. Wt.: 249.22

- O + O N O O CH3 H C CH3 3 O

+ O NH2 O CH3 Methyl -3-aminocrotonate(MAC) Benzylidine Derivative [C 5H9O2] Mol.Wt : 115.13 [C 12 H11 NO 5]

Methanol Glacial Acetic acid

CH3 O H3C O - O + O NH N

H3C

O O H3C

Nifedipine

[C 17 H18 N2O6] Mol.Wt : 346.34

MATERIAL BALANCE

Input Material Quantity Output Material Quantity(kg) (kg) Methyl Aceto Acetate 2250 Nifedipine 1000 Methanol 13700 Recovered methanol 13450 ONBA 1500 Recovered Acetic Acid 3100 Acetic Acid 3200 Solvent vapor loss 1750 Liquid Ammonia 1100 Effluent to ETP 2450 Total 21750 Total 21750

[6] QUETIAPINEHEMIFUMARATE

MANUFACTURING PROCESS

Dibenzo-(1,4)-thiazepine-11(10H) -one is condensed with 2-(2-(piperazin-1-yl)ethoxy)ethanol is treated with fumaric acid in presence of thionyl chloride and ethanol to give Quetiapine Hemifumarate. Fumaric acid, Thionyl chloride, Hydrochloric acid,Sodium hydroxide, Sodium Carbonate, Toluene, Ethanol, Activated Carbon and water are used as main raw materials. Reactions are carried out in reaction vessel.Ethanol and toluene are recovered and reused.SO2 and Hcl gas are scrubbed in the scrubbers and aqueous effluent is taken to ETP.

CHEMICAL REACTIONS

MATERIAL BALANCE

Input material Quantity Output material Quantity (KG) (KG) Dibenzo - (1,4)- thiazepine - 11 2780 Quetiapinehemifumarate 1000 (10H) one 3-Pyridyl Acetic Acid Fumaric acid 402 Recovered Toluene 6545 Thionyl chloride 50 Recovered Ethanol 7862 Hydrochloric acid 23 Spent Carbon 50 Sodium hydroxide 25 Solvent Vapor losses 103 Sodium Carbonate 300 Organic residue 1233

Toluene 7000 Material recovered for 1501 second crop Ethanol 8500 Sulphur Dioxide 27 (To scrubber) Activated Carbon 50 (To 30 scrubber) Water 11500 Effluent to ETP 12279 Total 30630 Total 30630 [7] FUROSEMIDE

MANUFACTURING PROCESS Stage-1 Charge Furfuryl Amine in the reactor at Room temperature.Charge Lasamide in the reactor at R. T.Stir the reaction mass for 1 hrs. Slowly heat the reaction mass up to 120 0 C. Maintain the reaction mass for 12 hrs between tem 120-123 0 C. After completion maintain.Cool the reaction mass up to 70-75 0C.Charge caustic solution in to the reaction mass keeping temperature between temp 70-75 0 C.Further cool the reaction mass to below 60 0 C.Charge IPA in to the reaction mass between temp 55-60 o C.Further cool the mass up to 30- 35 0C.Check pH in reaction mass, it should be 10.2 to 10.4.Maintain the reaction mass for 12 hrs between 28-35 oC.After 12 hrs maintain, reaction mass chilled to below 10 o C. Reaction mass maintain for 2 hrs between 0-10 0 C.Then reaction mass centrifuge .Give chilled IPA wash in the centrifuge up to clear ML. Stage-2 Charge D M water in to the reactor at R. T. Heat the D M water up to 55-60 0 C.Charge sodium;4-chloro-2-(furan-2-ylmethylamino)-5-sulfamoylbenzoate wet cake in the water at 55-60 0 C. Stir the mass for 10 min and check reaction mass for clear solution.Charge EDTA, Citric acid, Hydros and carbon in the reaction mass at 55-60 0 C.Stir the reaction mass for 10 min.Filter reaction mass through hyflow bed up to clear solution. Transfer reaction mass clear solution to another reactor.Add acetic acid in the reaction mass up to pH 4.5 to 4.6.Reaction mass is cooled to R.T.Stir the reaction mass for 30 min, then centrifuge it. Give D M Water up to sulphates& Chlorides NMT 300 ppm. Unload the cake in the centrifuge.Wet cake drying in the FBD up to below 05% w/w M/C. Then finally dry material milling in malt mill and packing is carried out.IPA is recovered and reused.

CHEMICAL REACTION:

MATERIAL BALANCE Input Material Quantity (Kg) Output material Quantity (kg) Lasamide 1300 Furosemide 1000 Furfuryl amine 2100 Recovered Isopropyl 4600 Alcohol Iso propyl Alcohol 4850 Organic Residue 3550 Caustic soda 600 Mother Liquor 25470 Citric acid 100 EDTA 10 Hydrose 10 Hyflow 150 Acetic Acid 500 water 25000 Total 34620 Total 34620 [8] RISERDRONATE SODIUM

MANUFACTURING PROCESS

Stage-1 A mixture of 3- pyridylacetic acid, H3PO3, diethyl carbonate we stirred for 5-10 minutes at room temperature. PCl3 was added drop wise between 25-35°C To the resulting reaction mixture; methanesulfonic acid was added drop wise between 40-55°C. Reaction mixture was heated to 60-65°C for 1.0-1.5h. Further the reaction mass was heated to 70-75°C for 4.0-6.0h. After reaction completion, pre chilled water (70 ml) was added at 65-80°C in a drop wise manner and diethyl carbonate layer was separated. To the resulting aqueous layer hydrochloric acid (10ml) was added and heated to reflux for 10-15hrs and cooled to 0- 15°C.Residronic acid was ejected; from the resulting aqueous reaction mass at a pH of 1.4- 1.8. The resulting suspension was filtered and slurred in water then dried to obtain Risedronic acid. Stage-2 Output from stage 1 is taken in DI Water and reacted with aqueous Sodium Hydroxide solution. The material is isolated in presence of Water, Isopropyl alcohol mixture to get form A of hemipenta-hydrate at 14-18°C and filtered at 0-5°C. Wet material is taken for reslurry water, Isopropyl alcohol at 14-18°C and filtered through PNF. Wet material is dried in FBD at 40-45°C with air 55±5 % RH to reach to LOD of 10-15 %. IPA is recovered and reused.Aqueous effluent is taken to ETP for treatment.

CHEMICAL REACTIONS:

MATERIAL BALANCE:

Input material Quantity (KG) Output material Quantity (KG)

3-Pyridyl Acetic Acid 2446 Risedronate Sodium 1000

Diethyl carbonate 750 Recovered Isopropyl 4500 alcohol Caustic soda lye 50 Material recovered 1359 for second crop Phosphorous trichloride 25 Hyflow + Carbon (Inorganic+organic 100 residue) Methane sulphonic Acid 500 Solvent Vapor losses 75 Isopropyl alcohol 5800 Organic residue 1795 Sodium hydroxide flakes 309 Effluent to ETP 10385 Hyflow 50 Activated carbon 50 Hydrochloric acid 220 Water (Distilled) 9011 Total 19211 Total 19211

[9] IOHEXOL/IOPAMIDOL/IODIXANOL

MANUFACTURING PROCESS 5- amino-2, 4, 6- Tri iodoisophthaloyl di chloride is treated with L-Acetoxy propionyl chloride to give Acetoxy compound. This compound is further treated with 2-Amino-1, 3-propanediol, & NaOH to give crude Iopamidol. The mass is c rystallized from IPA,filtered, and washed dried to give Iopamidol.

IOHEXOL: 5-amino – N, N (2, 3 Dihydroxy propyl & isophthalamide T riodo derivative is treated with 3- Chloro, 2 –propane diol. The product is cry stallized with IPA, filtered & dried to give Iohexol. Process involves reaction, purification and crystallisation.IPA is recovered and reused. Effluent is taken to ETP for treatment.

CHEMICAL REACTION:

MATERIAL BALANCE:

Input material Quantity Output material Quantity (KG) (KG) L-Acetoxy propionyl 1200 Iohexol 1000 chloride 5- amino -2, 4, 6 - Tri 1500 Recovered Isopropyl Alcohol iodoisophthaloyl di chloride 3850

2-Amino-1, 3- 1200 Solvent vapor losses (on 450 propanediol drying) Sodium Hydroxide 350 Effluent to ETP 2950 Isopropyl Alcohol 4000 Total 8250 Total 8250

[10] LAURYL PYRIDINIUM CHLORIDE

MANUFACTURING PROCESS Mixture of Lauryl Chloride & Pyridine reacts in SS reactor and heated slowly up to 900C Then Methyl Ethyl Ketone is added to reaction mass & heated slowly up to 800 C and 90% Methyl Ethyl Ketone is recovered from distillation. Then material is cooled & washed with acetone. Then 90% acetone recovered and material is th en dried & packed. Process involves reaction,distillation,washing, filteration and drying. Acetone ,Pyridine and methyl ethyl ketone are recovered and reused.

CHEMICAL REACTION:

,

MATERIAL BALANCE:

Input material Quantity (KG) Output material Quantity (KG) Lauryl chloride 722 Lauryl Pyridinium 1000 Chloride Pyridine 560 Recovered Pyridine 500

Methyl Ethyl ketone 4000 Recovered Methyl 3600 Ethyl ketone Acetone 2000 Recovered Acetone 1800 Solvent Vapor losses 202 Organic residue 200 Total 7282 Total 7282

[11 ] VILDAGLIPTIN

MANUFACTURING PROCESS Stage 1 Reaction of (2s)-1-(Chloroacetyl) -2-Cyanopyrrolidine (KSM-II) with 3 -Amino-1-Hydro- Xyadamantine (KSM-I) in presence of Potassium Carbonate and Dimethyl Formamide (DMF) as a solvent gives Vildagliptin crude.

Stage 2 Vildagliptin crude is purified by treatment of Aq. Potassium Hydrogen Sulphate and Aq. Potassium Carbonate in presence of Dichloromethane, followed by Acetone crystallization to give Vildagliptin API.

MDC,Acetone and DMF are recovered and reused.Aqueous effluent is taken to ETP for treatment. CHEMICAL REACTION:

MATERIAL BALANCE:

Input material Quantity (KG) Output material Quantity (KG) KSM I 770 Vildagliptin 1000

KSM II 720 Recovered Methylene 13440 Dichloride DMF 5400 Recovered Acetone 10120 Methylene dichloride 15000 Recovered DMF 5680

Potassium Carbonate 2600 Vapor losses through 1000 Vent Isopropyl Acetate 5040 Potassium 1200 Carbonate(cake) Sulphate 3750 Hyflow + charcoal 1600 Sodium chloride 630 Effluent to ETP 17420 Acetone 12500 Charcoal 50 Water 5000 Total 51460 Total 51460

[12] AMBROXOL HYDROCHLORIDE

MANUFACTURING PROCESS Ambroxol base is acidified with hydrochloric acid in IPA media in SS vessel and slowly heated up to 90⁰C - 95 ⁰C. Then Add carbon and filtration is done in sparkler filter. Chill to 10 -15 ⁰C then Centrifuging and drying is done. IPA i s sent for recovery and reused.Reactions are carried out in different stages.IPA is recovered and reused. Proc ess involves acidification,heating,filteration,cooling and centrifuging with drying and packing.

CHEMICAL REACTION:

MATERIAL BALANCE:

Input material Quantity (KG) Output material Quantity (KG) Ambroxol Base 912 Ambroxol 1000 Hydrochloride Isopropyl Alcohol 10500 Recovered Isopropyl 9500 Alcohol Activated Carbon 15 Evaporation losses 899 Spent Carbon 18 Organic residue 10

Total 11427 Total 11427

[13] PENTAPRAZOLE SODIUM

MANUFACTURING PROCESS Stage 1 2-Chloromethyl-3, 4-dimethoxy pyridine hydrochloride is reacted with 5-difluoromethoxy- 2-mercapto benzimidazole in isopropyl alcohol in presence of sodium hydroxide to get the Desired Product

Stage 2 Pantoprazole sulfide is treated with Sodium hypo chloride solution in IPA-water mixture at 0 to -5o C in presence of aqueous sodium hydroxide and after completion of reaction, the reaction mixture is quenched by the addition of aqueous sodium thiosulfate solution. To the resulting reaction mixture is added IPA and water and the reaction stirred for 30 minutes. The layers are separated. To the aqueous layer is added fresh IPA and the pH of the resulting reaction mixture is adjusted to 9 to 9.5 by the addition of acetic acid and stirred for 30 minutes. Layers are separated and the aqueous layer is again extracted with fresh IPA. The IPA extracts obtained after the pH adjustment are combined and concentrated up to about 3 times volume of the substrate. To the concentrated reaction mixture is added IPA to precipitate the product, which is filtered, and the obtained solid washed with IPA and dried to get Pentaprazole base.

Stage 3 Pentaprazole sodium is prepared by dissolving Pentaprazole base in Acetone and adding sodium hydroxide solution, some ethyl acetate is distilled out to get solid Pentaprazole sodium. After filtration and washing with acetone, pure Pentaprazole Sodium is obtained. Acetone and IPA are recovered and reused while aqueous effluent is taken to ETP .

CHEMICAL REACTION:

MATERIAL BALANCE:

Input material Quantity (KG) Output material Quantity (KG)

2-Chloromethyl-3-4-dimethox 770 Pentaprazole Sodium 1000 pyridine hydrochloride 5-difluoromethoxy-2-mercapto 740 Recovered Acetone 6168 benzimidazole Sodium Hydroxide 410 Recovered Isopropyl 11400 Alcohol Isopropyl Alcohol 11530 Evaporation losses 1337

Sodium Hypochlorite 2790 Effluent to ETP 9535 (10%aqueous) Acetone 6230 Water 6970 Total 29440 Total 29440 [14] MICONAZOLE NITRATE

MANUFACTURING PROCES

Stage 1 2, 4 DICHLORO PHENYL – 2 – IMIDAZOL – 1 – EHANOL Charge Toluene in reactor at R.T. Charge Sodium bicarbonate in reactor at R. T.Then charge imidazole in reactor and Tri Chloro Aceto Phenol at R.T.Close the man hole and stir the reaction mass for 15 minutes.Slowly heat to 50 0 C and maintain the reaction mass at 50-55 o C for 4 hours.Maintain for another 4 hours at 55 0 C and then at 60 0 C for 1 hour.Send the sample to Q.C. for check TLC for the absence of standing material.If TLC OK, then charge water in reaction mass and heat the reaction mass to 50-55 o C.Stir for 45 minutes at 50-55 o C. Keep reaction mass for 30 minutes for setting at 50-55 o C team.Separate out Aqueous layer at 50-55 o C. Again charge water in the reaction mass and.Keep the reaction mass for setting for 30 minutes at 50-55 o C .Again Separate out Aqueous layer at 50-55 o C.Charge Toluene and cool the reaction mass at R. T.Chill the reaction mass below 10 0 C .Start addition of sodium borohydride in reaction mass below 10 0 C.After the completion of addition maintain for 1 hour at 10 – 15 0 C.Raise reaction mass temp to R. T and maintain for 4 hours.Raise the temp to 40-45 0 C and maintain for 2 hours.Send the sample to Q.C. for TLC. If TLC OK. Apply cooling and charge water between 35-40 0 C.Cool the reaction mass to 25-30 0 C and maintain for 30 minutes.Centrifuge reaction mass and give toluene wash in centrifuge and unload wet cake and dry at 90 0 C.

Stage-2 CRUDE Charge Toluene, water and caustic soda flakes solution in reactor at R.T.Add TBAB at RT.Close the man hole and stir the reaction mass for 15 minutes.Then heat upto 50 0 C temp.Start addition of DCBC between temp 50-55 0 C and maintain for 4 hrs between temp 50-55 0 C.SenD the sample to Q. C. for Check by TLC. If TLC OK, settle the reaction mass for 30 minutes at 50-55 0 C. Separate out aqueous layer.Give water charge in reaction mass and heat to 50-55 0 C allow it to settle for 30 minutes. Separate out aqueous layers and check pH which should be Charge Hydrose and water solution in reaction mass and heat to 50-55 0 C and allow to settle for 30 minutes.Separate out aqueous layer.Again Charge water in reaction mass and heat to 50-55 0 C and allow to settle for 30 minutes at 50-55 0 C.Separate out aqueous layer.Transfer reaction mass to another reactor and heat to 60 0 C.Add carbon in reactor mass and stir for 30 minutes at 50-55 0 C and filter through sparker filter at 50-55 0 C temp.Clear filtrate is transferred to another clean reactor.Wash Toluene in sparker filter at 60 0 C and collect it in reactor. Reaction mass is cooled to R.T.Chill the reaction mass chill to 10-15 0 C. Slowly add Nitric acid to the reaction mass up to 3 pH at 10-150 C.Stir the reaction mass for 1 hrs at 10-15 0 C.Centrifuge reaction mass.Give toluene wash in centrifuge and unload wet cake.

Stage-3 PURE Charge Methanol in to the reactor at R.T.Charge Crude Mass in to the reactor at R. T. Close the man hole.Heat to reaction mass up to 60-65 0 C temp and maintain for one hr.Cool to R. T. after maintain completed.Chill the reaction mass to 10 0 C temp and maintain the reaction mass for one hrs below 10 0 C temp.Centrifuge giving D M water wash in the centrifuge and unload the wet cake.Dry,mill and Pack in fiber drum.

Toluene and methanol are recovered and reused.Aqueous effluent is taken to ETP.

CHEMICAL REACTION