Acetonitrile → 5-Bromo-6-methylpyridine-2-carbonitrile

Participants

Reaction Steps

Under an inert atmosphere, 3-bromo-6-iodo-2-methylpyridine (1 equiv) and acetonitrile were combined and stirred for 10 min, copper cyanide (0.5 equiv), sodium cyanide (0.8 equiv) and more acetonitrile were added. The reaction slurry was heated, with stirring, at 80° C. for 24 h. The reaction solution was cooled to room temperature and diluted with ammonium hydroxide (0.5 M aqueous solution). The mixture was stirred 15-30 min, filtered through diatomaceous earth and the filter cake was washed with ethyl acetate. The filtrate and wash were combined and further diluted with ethyl acetate and the solution was agitated for 15 min. The aqueous and organic phases were separated and the organic layer was washed sequentially with ammonium hydroxide (0.5 M aqueous solution; four times) and saturated aqueous sodium chloride (twice), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to provide 5-bromo-6-methylpicolinonitrile in 92% yield, as an off-white solid. MS (ESI) m/z 196.9 [M]+, 198.9 [M+2]+.

Provenance & Evidence