Propionitrile → 2-(3-Chloropyridin-2-yl)propanenitrile

Temperature

-78 °C

To a −78° C. solution of diisopropylamine (3.04 g, 4.28 mL, 30 mmol) was added n-butyl lithium (13.2 mL, 2.5M in hexane, 33 mmol). The reaction mixture was stirred for 20 minutes at −78° C., followed by the addition of propionitrile (1.65 g, 2.15 mL, 30 mmol). The reaction mixture was stirred for an additional 50 minutes, followed by the slow addition of 2-bromo-3-chloropyridine (1.92 g, 10 mmol) in THF (10 mL). The reaction was then allowed to warm to ambient temperature and stirred overnight. The reaction mixture was quenched with water and extracted with two portions of diethyl ether. The combined organic phases were washed with brine, concentrated, and the residue chromatographed on silica gel eluting with 30% ethyl acetate-hexane to obtain the title compound (1.52 g, 91%). 1H NMR (300 MHz, DMSO-d6) δ ppm 8.59 (dd, J=1.5, 4.7, 1H), 8.02 (dd, J=1.5, 8.1, 1H), 7.48 (dd, J=4.7, 8.1, 1H), 4.73 (q, J=7.1, 1H), 1.59 (d, J=7.1, 3H). MS (DCI) m/z 167 (M+H)+.

1. stirringThe reaction mixture was stirred for an additional 50 minutes
2. temperatureto warm to ambient temperature
3. stirringstirred overnight
4. customThe reaction mixture was quenched with water
5. extractionextracted with two portions of diethyl ether
6. washThe combined organic phases were washed with brine
7. concentrationconcentrated
8. customthe residue chromatographed on silica gel eluting with 30% ethyl acetate-hexane

ORD record

ord-c7eb4ef27b344bf1a8e754b2bb583da9

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08084616B2