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

A suspension of 21.9 g (335.35 mmol) of zinc in methanol (207 ml) was admixed at RT with 44 g (210.58 mmol) of 2,6-dichloro-5-fluoronicotinamide. Acetic acid (18.5 ml) was then added, and the mixture was heated to reflux while 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 hydrogencarbonate solution (414 ml) were added, followed by extraction by vigorous stirring. Subsequently, the reaction mixture was filtered with suction through kieselguhr and washed through 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 hydrogencarbonate solution (414 ml), dried and concentrated under reduced pressure. Dichloromethane (388 ml) was added to the crystals thus obtained, and extraction was effected by stirring for 20 min. The mixture was once more filtered with suction, washed through with diethyl ether and sucked dry.

1. temperaturethe mixture was heated
2. temperatureto reflux
3. customThe contents of the flask were then decanted off from the zinc, and ethyl acetate (414 ml) and saturated aqueous sodium hydrogencarbonate solution (414 ml)
4. additionwere added
5. extractionfollowed by extraction by vigorous stirring
6. filtrationSubsequently, the reaction mixture was filtered with suction through kieselguhr
7. washwashed through 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 hydrogencarbonate solution (414 ml)
11. customdried
12. concentrationconcentrated under reduced pressure
13. additionDichloromethane (388 ml) was added to the crystals
14. customthus obtained
15. extractionextraction
16. stirringby stirring for 20 min
17. filtrationThe mixture was once more filtered with suction
18. washwashed through with diethyl ether
19. customsucked dry

ORD record

ord-97df8a92da8a4194a53180ded1469674

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09096592B2