Dimethylformamide → 2-Amino-5-cyano-N,3-dimethylbenzamide

Temperature

130 °C

A flask purged with dry nitrogen was charged with palladium(II) acetate (370 mg, 1.64 mmol), 1,4-bis(diphenylphosphino)butane (850 mg, 2 mmol), activated zinc powder (500 mg, 7.64 mmol), zinc(II) cyanide (51 g, 434 mmol), and 2-amino-5-bromo-N,3-dimethylbenzamide (i.e. the product of Step A) (200 g, 820 mmol). Then freshly degassed N,N-dimethylformamide (500 mL) was added, and the mixture was heated at 130° C. for 25.5 h. Then the temperature was reduced to 95° C., and acetic acid (200 mL) was added. The mixture was sparged with nitrogen to remove hydrogen cyanide through scrubbers charged with aqueous sodium hydroxide and sodium hypochlorite solutions while cooling to room temperature. Then water (1500 mL) was added over 1.5 h, and sparging with nitrogen was continued overnight. Then the mixture was filtered, and the solids were washed with water and dried in a vacuum oven to afford the title compound as fluffy, light yellow solids, 141.5 g (90.9% yield).

1. customA flask purged with dry nitrogen
2. customwas reduced to 95° C.
3. customThe mixture was sparged with nitrogen
4. customto remove hydrogen cyanide through scrubbers
5. additioncharged with aqueous sodium hydroxide and sodium hypochlorite solutions
6. temperaturewhile cooling to room temperature
7. additionThen water (1500 mL) was added over 1.5 h
8. customsparging with nitrogen
9. filtrationThen the mixture was filtered
10. washthe solids were washed with water
11. customdried in a vacuum oven

ORD record

ord-19dff68585a343b5ac7ddefcf357ab96

Source dataset

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07528260B2