Pyridine → 2-Chloro-6-methylpyridine-4-carbonitrile

To a mixture of 2-chloro-6-methylpyridine-4-carboxamide (5.1 g, 30 mmol) obtained above, pyridine (7.3 mL, 90 mmol) and tetrahydrofuran (50 mL) was added dropwise a solution of trifluoroacetic anhydride (6.4 mL, 45 mmol) in tetrahydrofuran (10 mL) under ice-cooling, and the mixture was stirred under ice-cooling for 0.5 hr and at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure, aqueous sodium bicarbonate solution was added to the obtained residue, and the mixture was extracted with ethyl acetate. The combined organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=5/95→10/90). The obtained solution was concentrated under reduced pressure to give the title compound (4.3 g, 95%) as a colorless solid.

1. temperaturecooling
2. concentrationThe reaction mixture was concentrated under reduced pressure, aqueous sodium bicarbonate solution
3. additionwas added to the obtained residue
4. extractionthe mixture was extracted with ethyl acetate
5. washThe combined organic layer was washed with saturated brine
6. dry with materialdried over anhydrous magnesium sulfate
7. filtrationthe insoluble material was filtered off
8. concentrationThe filtrate was concentrated under reduced pressure
9. customthe obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=5/95→10/90)
10. concentrationThe obtained solution was concentrated under reduced pressure

ORD record

ord-49efeb532edc43a5b61b67c2dcd2cdc5

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09139589B2