Diethyl Ether → N-(5-(2,5-Dimethoxyphenyl)-4-methylthiazol-2-yl)-2,6-difluorobenzamide

Participants

Reaction Steps

Into a slurry of N,O-dimethylhydroxylamine hydrochloride (732 mg, 7.5 mmol) in CH2Cl2 (10.0 mL) at room temperature was added triethylamine (1.52 g, 15.0 mmol). The mixture was stirred at room temperature for 10 minutes, cooled to −78° C. Into the reaction mixture a solution of 2-(2,5-dimethoxyphenyl)acetyl chloride (1.08 g, 5.0 mmol) in CH2Cl2 (5.0 mL) was added dropwise. The mixture was gradually warm to room temperature. After 30 minutes at room temperature, the reaction mixture was quenched by slow addition of a solution of saturated NaHCO3, extracted with CH2Cl2. The extract was dried (Na2SO4), filtered and concentrated to the crude 32a (950 mg). The crude amide was taken up in THF (10.0 mL). Into the resulting solution at 0° C. was added dropwise a solution of 3M methylmagnesium bromide in ether (2.00 mL, 6.00 mmol). The mixture was stirred at room temperature for 3 hours, cooled to 0° C., quenched with ice. The mixture was acidified with 6N HCl. After 1 hour at room temperature, the mixture was neutralized with a solution of saturated NaHCO3, extracted with CH2Cl2. The extract was dried (Na2SO4), filtered and concentrated. The resulting methyl ketone was used directly without purification to prepare Compound 55 in the similar manner as described for the preparation of Compound 27.

Provenance & Evidence