2-Chloro-5-pyridineacetonitrile

Uses

2-Chloro-5-cyanomethylpyridine

Synthesis

General procedure for the synthesis of 2-chloro-5-pyridylacetonitrile from 2-chloro-5-chloromethylpyridine and sodium cyanide: Step 1. Synthesis of (6-chloropyridin-3-yl)acetonitrile. To a stirred solution of 2-chloro-5-chloromethylpyridine (25 g, 0.154 mol) in ethanol (40 mL) was slowly added an aqueous solution of sodium cyanide (8.17 g, 0.167 mol) (18 mL) at 0 °C. The reaction mixture was heated to reflux for 2 hours, followed by continued stirring at room temperature for 18 hours. Upon completion of the reaction, the solvent was removed by vacuum evaporation and the residue was dissolved in water and extracted with dichloromethane (500 mL). The organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica gel column chromatography with the eluent being a 70/30 dichloromethane/hexane solvent mixture to give 20 g (85% yield) of brown oily product. The product was solidified by standing and ESI-MS m/z 153 (MH+).

References

[1] Patent: WO2010/130708, 2010, A1. Location in patent: Page/Page column 105
[2] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 7, p. 2168 - 2173
[3] Patent: WO2013/13817, 2013, A1. Location in patent: Page/Page column 111
[4] Patent: WO2013/13815, 2013, A1. Location in patent: Page/Page column 221
[5] Patent: US2013/29961, 2013, A1. Location in patent: Paragraph 0705