Synthesis
Under nitrogen protection, sodium methanolate (0.41 g, 7.5 mmol) was dissolved in a 25 mL round bottom flask containing 10 mL of anhydrous N,N-dimethylformamide and the mixture was cooled to 4 °C using an ice water bath. Subsequently, 3-chloro-2-cyanopyridine (1.01 g, 7.2 mmol) was added to the reaction system, the ice-water bath was removed, and the reaction system was allowed to slowly warm up to 25 °C. After the reaction was carried out for 2 hours, the solvent was removed by vacuum concentration. Ethyl acetate was added to the concentrated residue and filtered to remove the insoluble precipitate. The filtrate was further concentrated on a rotary evaporator to afford the target product 2-cyano-3-methoxypyridine as a white solid (0.88 g, 88% yield), which could be used in subsequent reactions without further purification. The structure of the product was confirmed by 1H-NMR (CDCl3): δ 8.22 (dd, J = 7.4 and 1.6 Hz, 1H), 7.90 (dd, J = 7.5 and 7.3 Hz, 1H), 7.73 (dd, J = 7.73 and 1.6 Hz, 1H), 3.92 (s, 3H). Mass spectral analysis (ESI+) showed m/z (M + H)+ = 135.
References
[1] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 17, p. 5352 - 5359
[2] Patent: WO2015/187934, 2015, A1. Location in patent: Paragraph 0205
