methyl 3-amino-2-bromo-6-chlorobenzoate

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-amino-6-bromo-2-chloro-benzoic acid methyl ester (0.5 g, 1.89 mmol) in dioxane (10 ml) and water (1 ml) was added potassium carbonate (0.784 g, 5.67 mmol), PdCl2(dppf) (0.54 g, 0.189 mmol) and trimethyl boroxine (0.276 ml, 1.985 mmol). The mixture was stirred at 110° C. for 18 hours, then cooled to room temperature and filtered. The filtrate was concentrated to dryness under reduced pressure. Purification of the residue by flash chromatography (hexanes:EtOAc 8:2) gave 0.270 g (71%) of 5-amino-2-chloro-4-methyl-benzoic acid methyl ester as a tan solid. cooled to room temperature filtered The filtrate was concentrated to dryness under reduced pressure Purification of the residue by flash chromatography (hexanes:EtOAc 8:2)

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-amino-2-chloro-benzoic acid methyl ester (6.76 g, 36.4 mmol) in dichloromethane (100 mL) and methanol (50 mL) was added tetra-n-butylammonium tribromide (17.7 g, 36.4 mmol). The mixture was stirred at 25° C. for 90 minutes. Sodium thiosulfate (10% aqueous solution) was added and the mixture was extracted with dichloromethane. The combined extracts were washed with water, dried (Na2SO4), filtered, and concentrated to dryness under reduced pressure. The crude material was purified by flash column chromatography (hexane/acetone 8:2). Fractions with the desired product were concentrated to small volume. The resulting suspension was allowed to stand for two hours and was then filtered to obtain 5-amino-6-bromo-2-chloro-benzoic acid methyl ester as a white solid (2.7 g, 28%). the mixture was extracted with dichloromethane The combined extracts were washed with water dried (Na2SO4) filtered concentrated to dryness under reduced pressure The crude material was purified by flash column chromatography (hexane/acetone 8:2) Fractions with the desired product were concentrated to small volume to stand for two hours was then filtered