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 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 the mixture was stirred 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. filtrationSubsequently, the reaction mixture was filtered with suction through kieselguhr
6. washwashed through three times with ethyl acetate (517 ml each time)
7. customThe organic phase was removed
8. washthe aqueous phase was washed with ethyl acetate (258 ml)
9. washThe combined organic phases were washed once with saturated aqueous sodium hydrogencarbonate solution (414 ml)
10. customdried
11. concentrationconcentrated under reduced pressure
12. additionDichloromethane (388 ml) was added to the crystals
13. customthus obtained
14. stirringthe mixture was stirred for 20 min
15. filtrationThe mixture was once more filtered with suction
16. washwashed through with diethyl ether
17. customsucked dry

ORD record

ord-3de2b2b4324a4daab5b9a3dc9abb0bf5

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08765769B2