Pyridine → N-methoxy-N-methyl-6-(trifluoromethyl)nicotinamide

Participants

Reaction Steps

To a stirred mixture of N,O-dimethylhydroxylamine hydrochloride (9.47 g, 97.1 mmol) and pyridine (18.6 mL, 230 mmol) in CH2Cl2 (100 mL) was added a solution of 6-(trifluoromethyl)nicotinoyl chloride (18.50 g, 88.28 mmol) in CH2Cl2 (250 mL) over 3-5 min. The reaction mixture was stirred at rt overnight, and then carefully quenched with 150 mL of saturated aq. NaHCO3 solution and stirred for about 1 hr. The mixture was diluted with CH2Cl2 (50 mL) and the organic phase was separated and washed with aq. NaHCO3 solution (100 mL) and brine (50 mL), dried (Na2SO4), filtered, and evaporated. The residue was redissolved in toluene (about 50 mL) and evaporated again to azeotrope the pyridine off. This was repeated with toluene (about 50 mL). The product was isolated as a colorless oil (with a small amount of crystalline material) (19.1 g, 92%).

Provenance & Evidence