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 from the zinc, ethyl acetate (414 ml) and saturated aqueous sodium bicarbonate solution (414 ml) were added and the mixture was stirred vigorously. The mixture was then filtered off with suction through kieselguhr and washed three times with ethyl acetate (517 ml each). 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 bicarbonate solution (414 ml), dried and concentrated under reduced pressure. Dichloromethane (388 ml) was added to the crystals obtained in this manner, and the crystals were triturated for 20 min. The crystals were once more filtered off with suction and washed with diethyl ether and sucked dry.

1. temperaturethe mixture was heated
2. temperatureat reflux
3. customThe contents of the flask were then decanted from the zinc, ethyl acetate (414 ml) and saturated aqueous sodium bicarbonate solution (414 ml)
4. additionwere added
5. stirringthe mixture was stirred vigorously
6. filtrationThe mixture was then filtered off with suction through kieselguhr
7. washwashed three times with ethyl acetate (517 ml each)
8. customThe organic phase was separated off
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 crystals
14. customobtained in this manner
15. customthe crystals were triturated for 20 min
16. filtrationThe crystals were once more filtered off with suction
17. washwashed with diethyl ether
18. customsucked dry

ORD record

ord-6326fe2013b84368bf620e794c8fe9f7

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09216978B2