Methylamine → 4-Chloro-N-methylpicolinamide

Participants

Reaction Conditions

Reaction Steps

A suspension of 17.8 g (0.103 mol, 1 eq) of 4-chloro-pyridine-2-carboxylic acid methyl ester hydrochloride in 15 mL of methanol was cooled to 0° C. and slowly treated with a 2.0 M solution of methylamine in tetrahydrofuran at a rate that kept internal temperature below 5° C. The reaction mixture was stirred at 0° C. for 2 hours, then slowly allowed to warm up to ambient temperature and stirred for 18 hours. Solvent was removed in vacuum, approx. 200 mL of ethyl acetate was added and the resulting suspension was filtered. The precipitate was washed with 100 mL of ethyl acetate. The combined ethyl acetate solutions were washed three times with 100 mL of brine and dried over sodium sulfate. Solvent was removed in vacuum to yield 14.16 g of the product as orange oil. Yield: 80.5%.

Provenance & Evidence