Acetic Acid → 2-Chloro-5-fluoropyridine-3-carboxamide

At RT, 44 g (210.58 mmol) of 2,6-dichloro-5-fluoronicotinamide were added to a suspension of 21.9 g (335.35 mmol) of zinc in methanol (207 ml). Acetic acid (18.5 ml) was then added, and the mixture was heated at reflux with stirring for 24 h. The contents of the flask were then decanted off from the zinc, and ethyl acetate (414 ml) and saturated aqueous sodium bicarbonate solution (414 ml) were added, followed by extraction with vigorous stirring. Subsequently, the reaction mixture was filtered with suction through kieselguhr, and the filter cake was washed three times with ethyl acetate (517 ml each time). The organic phase was removed and the aqueous phase was washed with ethyl acetate (258 ml). The combined organic phases were washed once with saturated aqueous sodium bicarbonate solution (414 ml), dried and concentrated under reduced pressure. Dichloromethane (388 ml) was added to the solid obtained in this manner, and extraction was effected by stirring for 20 min. The mixture was once more filtered off with suction, and the filter cake was washed with diethyl ether and sucked dry.

1. temperaturethe mixture was heated
2. temperatureat reflux
3. customThe contents of the flask were then decanted off from the zinc, and ethyl acetate (414 ml) and saturated aqueous sodium bicarbonate solution (414 ml)
4. additionwere added
5. extractionfollowed by extraction with vigorous stirring
6. filtrationSubsequently, the reaction mixture was filtered with suction through kieselguhr
7. washthe filter cake was washed three times with ethyl acetate (517 ml each time)
8. customThe organic phase was removed
9. washthe aqueous phase was washed with ethyl acetate (258 ml)
10. washThe combined organic phases were washed once with saturated aqueous sodium bicarbonate solution (414 ml)
11. customdried
12. concentrationconcentrated under reduced pressure
13. additionDichloromethane (388 ml) was added to the solid
14. customobtained in this manner, and extraction
15. stirringby stirring for 20 min
16. filtrationThe mixture was once more filtered off with suction
17. washthe filter cake was washed with diethyl ether
18. customsucked dry

ORD record

ord-9b3531eda91649f5a50a97c885acb6e8

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09090610B2