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 with stirring at reflux for 24 h. The contents of the flask were then decanted from the zinc, and ethyl acetate (414 ml) and saturated aqueous sodium hydrogen carbonate solution (414 ml) were added, followed by intense extractive stirring. Subsequently the reaction mixture was filtered with suction through kieselguhr and the filter product was washed three times with ethyl acetate (517 ml each time). The organic phase was separated off and the aqueous phase was washed with ethyl acetate (258 ml). The combined organic phases were washed once with saturated aqueous sodium hydrogen carbonate solution (414 ml), dried and concentrated under reduced pressure. Dichloromethane (388 ml) was added to the crystals obtained in this manner, and the mixture was stirred for 20 min. The mixture was once more filtered off with suction, washed with diethyl ether and sucked dry.

1. temperaturethe mixture was heated
2. temperatureat reflux for 24 h
3. customThe contents of the flask were then decanted from the zinc, and ethyl acetate (414 ml) and saturated aqueous sodium hydrogen carbonate solution (414 ml)
4. additionwere added
5. filtrationSubsequently the reaction mixture was filtered with suction through kieselguhr
6. washthe filter product was washed three times with ethyl acetate (517 ml each time)
7. customThe organic phase was separated off
8. washthe aqueous phase was washed with ethyl acetate (258 ml)
9. washThe combined organic phases were washed once with saturated aqueous sodium hydrogen carbonate solution (414 ml)
10. customdried
11. concentrationconcentrated under reduced pressure
12. additionDichloromethane (388 ml) was added to the crystals
13. customobtained in this manner
14. stirringthe mixture was stirred for 20 min
15. filtrationThe mixture was once more filtered off with suction
16. washwashed with diethyl ether
17. customsucked dry

ORD record

ord-b76ddeaab5da40bc8227c3edeee74663

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09266885B2