2-(5-Methylpyridin-2-yl)acetonitrile

3510-66-5

38203-08-6

Step 3 - Preparation of 2-(5-methylpyridin-2-yl)acetonitrile: To a solution of anhydrous acetonitrile (10.1 mL, 191.83 mmol, 3.3 eq.) in anhydrous tetrahydrofuran (500 mL) was added slowly and dropwise at -78 °C a solution of n-butyllithium (2.5 M, 69.8 mL, 174.39 mmol, 3 eq.) in hexanes, protected by nitrogen. The resulting white suspension was stirred at -78 °C for 1 h. Anhydrous tetrahydrofuran (30 mL) solution of 2-bromo-5-methylpyridine (10.0 g, 58.13 mmol, 1 eq.) was added. The reaction mixture was kept at -78 °C for 1 h, followed by a slow warming to room temperature and continued stirring for 1 h. The reaction was completed by the addition of ice water. Upon completion of the reaction, the reaction was quenched by the addition of ice water and layered. The organic layer was washed sequentially with water and brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give 18 g of crude product. The crude product was purified by silica gel column chromatography (eluent: petroleum ether/ethyl acetate=15:1) to afford 2-(5-methylpyridin-2-yl)acetonitrile (6.2 g, 80% yield).1H NMR (300 MHz, CDCl3): δ 8.40 (d, J=3.0 Hz, 1H), 7.54 (dd, J1=3.0 Hz, J2=6.0 Hz. 1H), 7.32 (d, J=6.0 Hz, 1H), 3.90 (s, 2H), 2.40 (s, 3H).