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

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]+.

1. temperatureThe reaction slurry was heated
2. stirringwith stirring, at 80° C. for 24 h
3. stirringThe mixture was stirred 15-30 min
4. filtrationfiltered through diatomaceous earth
5. washthe filter cake was washed with ethyl acetate
6. washThe filtrate and wash
7. additionfurther diluted with ethyl acetate
8. stirringthe solution was agitated for 15 min
9. customThe aqueous and organic phases were separated
10. washthe organic layer was washed sequentially with ammonium hydroxide (0.5 M aqueous solution; four times) and saturated aqueous sodium chloride (twice),
11. dry with materialdried over anhydrous sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated under reduced pressure

ORD record

ord-515bf039147e41aea8851f4fff9fb343

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08569494B2