Acetamide → 2-Chloro-5,6-difluoronicotinamide

To a mixture of 2-chloro-5,6-difluoronicotinonitrile (89.66 g, 514 mmol), acetamide (66.8 g, 1130 mmol), THF (337.5 mL), and water (113 mL) was added palladium(II) chloride (1.822 g, 10.27 mmol) with stirring. The reaction mixture was stirred at 60° C. for 18 hours under a nitrogen atmosphere. The reaction mixture was subsequently cooled to room temperature and was added to a stirred mixture of EtOAc (900 mL), hexane (90 mL) and water (180 mL). The layers were allowed to separate and the aqueous layer was removed. The organic layer was washed with water (180 mL) and concentrated on a rotary evaporator at 29° C. to afford an oil that solidified. The solid was suspended in hexanes (270 mL) and filtered after 1 hour. The flask was rinsed forward with hexanes (50 mL). The filter cake was washed with additional hexanes (20 mL) and dried in a vacuum oven at 40° C. to give the title compound as a light tan solid (82.21 g, 83%). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.93 (s br, 1H), 8.10 (s br, 1H), 8.32-8.37 (m 1H).

1. stirringThe reaction mixture was stirred at 60° C. for 18 hours under a nitrogen atmosphere
2. customto separate
3. customthe aqueous layer was removed
4. washThe organic layer was washed with water (180 mL)
5. concentrationconcentrated on a rotary evaporator at 29° C.
6. customto afford an oil that solidified
7. filtrationfiltered after 1 hour
8. washThe flask was rinsed forward with hexanes (50 mL)
9. washThe filter cake was washed with additional hexanes (20 mL)
10. customdried in a vacuum oven at 40° C.

ORD record

ord-402fffc22e804bf28a2d822a4fad55f6

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09056873B2