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

Temperature

95 °C

A 1-L, three-neck, round-bottom flask equipped with a mechanical stirrer and a nitrogen inlet was charged with 3,6-dibromo-2-methylpyridine (150 g, 0.59 mol), copper (I) cyanide (42.8 g, 0.47 mol) and sodium cyanide (23 g, 0.47 mol). To the mixture was added N,N-dimethylformamide (300 mL). The mixture was heated to 95° C. and stirred for 48 h. The reaction mixture was cooled to ambient temperature and poured into ethanol (3 L) while stirring. The mixture was filtered through a pad of Celite, the filtrate was concentrated under reduced pressure and partitioned between water (3 L) and ethyl acetate (3 L). The organic layer was separated and washed with brine (2×600 mL), dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica gel plug purification (0-5% ethyl acetate in hexanes) to afford the product (61.5 g, 45% yield) as a white solid. In addition, 19.32 g (14%) of the mixture of the starting material and the product was isolated.

1. temperatureThe reaction mixture was cooled to ambient temperature
2. stirringwhile stirring
3. filtrationThe mixture was filtered through a pad of Celite
4. concentrationthe filtrate was concentrated under reduced pressure
5. custompartitioned between water (3 L) and ethyl acetate (3 L)
6. customThe organic layer was separated
7. washwashed with brine (2×600 mL)
8. dry with materialdried over anhydrous sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customThe crude product was purified by silica gel plug purification (0-5% ethyl acetate in hexanes)

ORD record

ord-f60477686b594c61a4577b790b2c90e2

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09193692B2