3,5-Bis(trifluoromethyl)benzyl bromide → Imnopitant

Participants

Reaction Steps

To a solution of 750 mg (2.32 mmol) N-methyl-6-(4-methyl-piperazin-1-yl)-4-o-tolyl-nicotinamide in 16 ml tetrahydrofuran, 3 ml of a 1 M solution (3 mmol) of potassium hexamethyldisilazide in tetrahydrofuran was added at room temperature. After 1 h, 0.43 ml (2.3 mmol) 3,5-bis(trifluoromethyl)benzyl bromide was added dropwise to the resulting suspension. The reaction was quenched with water after 1 h and the mixture was extracted with three 20 ml portions of ethyl acetate. The combined organic extracts were washed with saturated aqueous sodium chloride solution, dried with sodium sulfate and concentrated. Column chromatography gave 950 mg (74%) N-(3,5-bis-trifluoromethyl-benzyl)-N-methyl-6-(4-methyl-piperazin-1-yl)-4-o-tolyl-nicotinamide. The white foam was dissolved in a small amount of diethyl ether and treated with 2 ml 3 N hydrochloric acid solution in diethyl ether. Concentration afforded 1.02 g (74%) of the title compound as a white solid.

Provenance & Evidence