Methanamine, N-methoxy-, hydrochloride (1:1) → N-methoxy-N-methyl-2-phenylamino-6-trifluoromethyl-nicotinamide

Participants

Reaction Conditions

Reaction Steps

A solution of 2-phenylamino-6-trifluoromethyl-nicotinic acid (6.2 g, 22.0 mmol), N,O-dimethylhydroxylamine hydrochloride (2.79 g, 28.6 mmol) and 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (13.3 g, 35.2 mmol) in N,N-dimethylformamide (120 mL) was treated with N,N-diisopropylethylamine (8.88 g, 12 mL, 68.7 mmol). The reaction mixture was stirred at 25° C. for 4 h. At this time, the reaction was diluted with methylene chloride (400 mL), washed with a saturated aqueous ammonium chloride solution (1×300 mL), a saturated aqueous sodium bicarbonate solution (1×300 mL), and a saturated aqueous sodium chloride solution (1×200 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Flash chromatography (250 g silica column, 10-35% ethyl acetate/hexanes) afforded N-methoxy-N-methyl-2-phenylamino-6-trifluoromethyl-nicotinamide (6.86 g, 96%) as a brown oil which upon trituration with ether became a brown solid.

Provenance & Evidence