Acetic Acid → 4-(Trifluoromethyl)benzamide

Participants

Reaction Steps

2-Methoxy-6-methylsulfanyl-N-(2-oxo-cyclohexyl)-4-trifluoromethyl-benzamide (intermediate B, 380 mg, 1.05 mmol) was dissolved in 10 mL tetrahydrofurane. Acetic acid (145 mg, 2.4 mmol) and pyrrolidine (97 mg, 1.4 mmol) were added and the reaction mixture was stirred 1 h at room temperature. Sodium triacetoxyborohydride (290 mg, 1.4 mmol) was added and stirring was continued at room temperature overnight. The mixture was extracted with 2N sodium carbonate solution and ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. Purification of the residue by flash chromatography on silica gel (dichloromethane/methanol/ammonia 100:0:0->140:10:1) yielded cis-2-methoxy-6-methylsulfanyl-N-2-pyrrolidin-1-yl-cyclohexyl)-4-trifluoromethyl-benzamide as a light yellow solid (125 mg, 28%), MS: m/e=417.3 [(M+H)] and trans-2-methoxy-6-methylsulfanyl-N-2-pyrrolidin-1-yl-cyclohexyl)-4-trifluoromethyl-benzamide as a light yellow solid (28 mg, 6%), MS: m/e=417.3 [(M+H)+].

Provenance & Evidence