4-Acetylamino-5-Chloro-2-Hydroxybenzoic Acid Methyl Ester

To a stirred solution of methyl 4-acetylamino-2-hydroxy benzoate (61.4 grams, 294.0 mmol, obtained in above step) in dichloroethane (1.2 L) was added N- chlorosuccinimide (58.8 grams, 441 mmol) and the reaction mixture was refluxed for 3 hours. The volatiles were removed under reduced pressure; the solid compound thus precipitated was diluted with water (1.0 L) and filtered. The crude product was diluted with a 1 :9 mixture (methanol and dichloromethane) and washed with brine. The organic layer was dried over anhydrous sodium sulphate and the volatiles were removed under reduced pressure to obtain methyl 4-acetylamino-5-chloro-2-hydroxy benzoate (67.7 grams).Yield: 94.6 percent.Ή - NMR (DMSO-dTo a stirred solution of methyl 4-acetylamino-2-hydroxy benzoate (61.4 grams, 294.0 mmol, obtained in above step) in dichloroethane (12 L) was added N-chlorosuccinimide (58.8 grams, 441 mmol) and the reaction mixture was refluxed for 3 hours. N-Chlorosuccinimide (NCS) (69 grams, 0.509 mole) was added to a stirred solution of methyl 4-acetylamino-2-hydroxy benzoate (88.8 grams, 0.424 mole, obtained in the above step) in 1 , 2-dichloroethane (2 L) at RT. Reaction mass was slowly heated to 80 °C and stirred further for 4 hours at the same temperature, while monitoring the progress of the reaction by TLC. The mass was cooled to RT and 1 , 2-dichloroethane was evaporated. The residue was diluted with water (1L) and the solid obtained was filtered.The solid obtained was dissolved in DCM (2 L) and washed with brine solution (500 mL). The organic phase was dried over Na3 (160 g, 0.776 mol) and ethyl acetate (1100 mL) were added to a 2 L three-necked flask and sulfuryl chloride (134.5 g, 0.995 mol) was added dropwise at -5 to 0 ° C and the temperature was controlled at -5 to 0 ° C for about 1 h Within the drop completed. After the addition was completed, stirring was continued for 1 h and the reaction was monitored by TLC. After the reaction was completed, the reaction solution was poured into water, With 10mol / L sodium hydroxide solution to adjust the pH 4 ~ 5, suction filtration, The filtrate was extracted to separate the organic layer, the organic layer was spin-dried, A large amount of solid was obtained, which was combined with the filter cake solids, heated with 5 times ethanol hot beating 30min, suction filtered, the filter cake was dried, 151.1 g of a white solid was obtained in a yield of 80percent and a purity of 98.7percentStage 3; Methyl 4-(acetylamino)-5-chloro-2-hydroxybenzoate; Methyl 4-(acetylamino)-2-hydroxybenzoate (1.0 eq.) was suspended in 12 vol ethyl acetate at TA stirred suspension of methyl 4-(acetylamino)-5-chloro-2- (methyloxy)benzoate (103g, 0.4mol) in dry DCM (460ml) was cooled to 0To a 50 mL three-necked flask was added 4 (64 g, 0.263 mol) and N, N-dimethylformamide (510 mL) under stirring, NBS (61 g, 0.342 mol) was added at room temperature, The reaction was continued under this condition and the reaction was monitored by TLC.After completion of the reaction, water was added 400mL, suction filtration, The filter cake was washed with water several times, the filter cake was collected dry 67.5g white solid, yield 79.5%, purity 92.4%

Molecular Weight:243.64
XLogP3:1.8
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:243.0298355
Monoisotopic Mass:243.0298355
Topological Polar Surface Area:75.6
Heavy Atom Count:16
Complexity:284
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes