Hydrochloric Acid → N-[2-(3,4-dimethoxyphenyl)ethyl]-3-difluoromethoxy-2-(4-chlorophenyl)acrylamide

Participants

Reaction Steps

Five hundred milligrams (500 mg) of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-chlorophenyl)acrylamide (1.33 mmol), 2.00 g (3.56 mmol) of 10% aqueous potassium hydroxide solution, 87 mg (0.266 mmol) of tetrabutylammonium bromide and 10 ml of ethylene glycol dimethyl ether were mixed and chlorodifluoromethane gas was blown thereto at room temperature. After a sample was taken out from the reaction mixture and the disappearance of the starting material was confirmed by thin layer chromatograph analysis, 5% hydrochloric acid was added to the reaction mixture. The reaction mixture was extracted with ethyl acetate, washed with 5% hydrochloric acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=2:1) and the obtained residue was washed with hexane to give 360 mg of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-difluoromethoxy-2-(4-chlorophenyl)acrylamide.

Provenance & Evidence