Hydrochloric Acid → 2-(Difluoromethoxy)-N-methoxy-N-methyl-3-pyridinecarboxamide

Participants

Reaction Steps

N-methoxy-N-methyl-2-hydroxynicotinamide (500 mg, 2.76 mmol), sodium chlorodifluoroacetate (505 mg, 3.31 mmol), and sodium hydroxide (132 mg, 3.31 mmol) were added to N,N-dimethylformamide (1.4 mL). The resultant mixture was stirred at 125° C. overnight under an argon atmosphere. The reaction solution was cooled down to room temperature, added with 1N hydrochloric acid and water, and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, concentrated in vacuo, and purified using preparative thin-layer chromatography (chloroform/methanol=9/1). N-methoxy-N-methyl-2-difluoromethoxynicotinamide (341 mg, yield 53%) was obtained as a yellow oil.

Provenance & Evidence