Triethylamine → 4-(4-chloro-2-fluorophenyl)-N-methylnicotinamide

Participants

Reaction Steps

To a solution of 4-(4-chloro-2-fluorophenyl)nicotinic acid (2 g, 7.95 mmol in dichloromethane (40 mL) cooled to 0° C. was added oxalyl chloride (2.09 mL, 23.8 mmol) followed by DMF (2 mL). The reaction mixture was allowed to warm to room temperature and stirred for 2 h. The reaction mixture was concentrated under reduced pressure and treated with dichloromethane (25 mL). This solution was added to a mixture of methylamine hydrochloride (5.37 g, 79 mmol) and triethylamine (11.08 mL, 79 mmol) in dichloromethane (25 mL) cooled to 0° C. The resultant mixture was stirred at room temperature for 3 h and then washed with a saturated solution of sodium bicarbonate. The organic layer was separated, dried (Na2SO4) and concentrated under reduced pressure to afford 4-(4-chloro-2-fluorophenyl)-N-methylnicotinamide (1.3 g, 4.91 mmol, 62%) as an off-white solid. LC/MS (ESI) m/e 265.1 [(M+H)+, calcd for C13H11ClFN2O 265.1]; LC/MS retention time (method C): tR=1.69 min.

Provenance & Evidence