methyl 3-bromo-5-chlorobenzoate

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirring mixture of 5-methylthiazole (4.37 g, 44.1 mmol) in dry THF (30 L) under was added n-BuLi (44.1 mmol, 17.64 ml solution in hexanes) drop wise over 10 minutes at −78° C. under nitrogen atmosphere. The mixture was stirred between −78° C. and −60° C. for 30 minutes and then cooled to −78° C. A solution of 3-Bromo-5-chloro-benzoic acid methyl ester (11.0 g, 44.1 mmol) in THF (20 mL) was added drop wise over 10 minutes. The resulting mixture was stirred at −78° C. for 30 minutes and warmed to room temperature with stirring overnight. The mixture was cooled to 0° C. and treated with water (50 mL). The resulting mixture was adjusted to pH around 6 with HCl (1N) and extracted with EtOAc (100 mL×3). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with petroleum ether/EtOAc mixtures to afford (3-Bromo-5-chloro-phenyl)-(5-methyl-thiazol-2-yl)-methanone (14 g, yield=100%) as a solid. The resulting mixture was stirred at −78° C. for 30 minutes warmed to room temperature with stirring overnight The mixture was cooled to 0° C. extracted with EtOAc (100 mL×3) The combined organic layers were dried over Na2SO4 filtered concentrated under reduced pressure The residue was purified by silica gel column chromatography eluting with petroleum ether/EtOAc

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirring mixture of 5-methylthiazole (4.37 g, 44.1 mmol) in dry THF (30 L) under was added n-BuLi (44.1 mmol, 17.64 ml solution in hexanes) drop wise over 10 minutes at −78° C. under nitrogen atmosphere. The mixture was stirred between −78° C. and −60° C. for 30 minutes and then cooled to −78° C. A solution of 3-Bromo-5-chloro-benzoic acid methyl ester (11.0 g, 44.1 mmol) in THF (20 mL) was added drop wise over 10 minutes. The resulting mixture was stirred at −78° C. for 30 minutes and warmed to room temperature with stirring overnight. The mixture was cooled to 0° C. and treated with water (50 mL). The resulting mixture was adjusted to pH around 6 with HCl (1N) and extracted with EtOAc (100 mL×3). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with petroleum ether/EtOAc mixtures to afford (3-Bromo-5-chloro-phenyl)-(5-methyl-thiazol-2-yl)-methanone (14 g, yield=100%) as a solid. The resulting mixture was stirred at −78° C. for 30 minutes warmed to room temperature with stirring overnight The mixture was cooled to 0° C. extracted with EtOAc (100 mL×3) The combined organic layers were dried over Na2SO4 filtered concentrated under reduced pressure The residue was purified by silica gel column chromatography eluting with petroleum ether/EtOAc