methyl 2-amino-5-bromo-4-chlorobenzoate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-Amino-5-bromo-4-chloro-benzoic acid methyl ester (2.08 g, 7.86 mmol) and pyridine (1.91 ml, 23.6 mmol) in dichloromethane (75.0 ml) was added 1.00N isopropylchloroformate in toluene dropwise. The mixture was stirred for 16 hours at room temperature. The mixture washed with 0.500N HCl(aq) (100 ml), and brine (3×100 ml), then dried (Na2SO4) and concentrated to an oil. Purification by silica gel chromatography (gradient eluent, 0-10% ethyl acetate in hexane) provided 5-Bromo-4-chloro-2-isopropoxycarbonylamino-benzoic acid methyl ester (2.53 g, 92%) as a white crystalline material. MS (ES+): 350, 352 (M+H). The mixture washed with 0.500N HCl(aq) (100 ml), and brine (3×100 ml) dried (Na2SO4) concentrated to an oil Purification by silica gel chromatography (gradient eluent, 0-10% ethyl acetate in hexane)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-Amino-5-bromo-4-chloro-benzoic acid methyl ester (2.08 g, 7.86 mmol) and pyridine (1.91 ml, 23.6 mmol) in dichloromethane (75.0 ml) was added 1.00N isopropylchloroformate in toluene dropwise. The mixture was stirred for 16 hours at room temperature. The mixture washed with 0.500N HCl(aq) (100 ml), and brine (3×100 ml), then dried (Na2SO4) and concentrated to an oil. Purification by silica gel chromatography (gradient eluent, 0-10% ethyl acetate in hexane) provided 5-Bromo-4-chloro-2-isopropoxycarbonylamino-benzoic acid methyl ester (2.53 g, 92%) as a white crystalline material. MS (ES+): 350, 352 (M+H). The mixture washed with 0.500N HCl(aq) (100 ml), and brine (3×100 ml) dried (Na2SO4) concentrated to an oil Purification by silica gel chromatography (gradient eluent, 0-10% ethyl acetate in hexane)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-Amino-4-chloro-benzoic acid methyl ester (1.85 g, 10.0 mmole) in HOAc (20.0 ml) was injected bromine (0.512 ml, 10.0 mmole) dropwise. The reaction was stirred at room temperature for an hour. The mixture was diluted with ethyl ether (200 ml) and then the solvents were decanted. The residue was partitioned between ethyl acetate (200 ml) and 0.100N NaOH(aq) (200 ml). After separated the two layers, the organic layer was dried over Na2SO4, filtered and concentrated to provide the crude product (2.08 g, 78%), which was used directly for the next step without further purification. MS (ES+): 264, 266 (M+H). the solvents were decanted The residue was partitioned between ethyl acetate (200 ml) and 0.100N NaOH(aq) (200 ml) After separated the two layers the organic layer was dried over Na2SO4 filtered concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 2-amino-4-chlorobenzoate (20.0 g, 108 mmol) in DMF (200 mL) was added N-bromosuccinimide (19.2 g, 108 mmol) in one portion and stirred overnight at room temperature. The resulting solids were filtered off and dissolved in toluene, dried with Na2SO4, and concentrated to give methyl 2-amino-5-bromo-4-chlorobenzoate (26.47 g, 93%) The resulting solids were filtered off dissolved in toluene dried with Na2SO4 concentrated