Acetonitrile → 2-(6-Methoxypyridin-2-yl)acetonitrile

Temperature

-78 °C

1.6M n-Butyllithium/hexane solution (300 mL, 479.43 mmol) was added to a solution of acetonitrile (21.87 g, 532.70 mmol) in THF (630 mL) at −78° C. under argon atmosphere, and the mixture was stirred at −78° C. for 30 min. 2-Bromo-6-methoxypyridine (25.04 g, 133.18 mmol) was added dropwise thereto over 15 min at −78° C., and the reaction mixture was stirred at room temperature for 4 hr. The reaction mixture was poured into ice water (900 mL), and the mixture was extracted with ethyl acetate (×3). The organic layer was washed with water and brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 2→20% ethyl acetate/hexane) to give 2-(6-methoxypyridin-2-yl)acetonitrile (11.37 g, 77 mmol, 58%) as a colorless oil.

1. waitover 15 min at −78° C.
2. stirringthe reaction mixture was stirred at room temperature for 4 hr
3. extractionthe mixture was extracted with ethyl acetate (×3)
4. washThe organic layer was washed with water and brine
5. dry with materialdried over magnesium sulfate
6. customthe solvent was evaporated under reduced pressure
7. customThe obtained residue was purified by silica gel column chromatography (solvent gradient; 2→20% ethyl acetate/hexane)

ORD record

ord-261c817bcb0f409b93eb8660436bb3f8

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365520B2