Synthesis
General procedure for the synthesis of 4-cyano-2-methoxypyridine from 2-chloro-4-cyanopyridine and sodium methanol: To a solution of 2-chloro-4-cyanopyridine (1.38 g, 10 mmol) in dioxane (10 mL) was added a methanolic solution of sodium methanol (25%, 2.27 g, 10.5 mmol). The reaction mixture was heated to reflux for 5 h, followed by cooling to room temperature and standing overnight in a refrigerator. The precipitate was collected by filtration and washed with methanol. The filtrate was concentrated to about 10 mL and water (100 mL) was added. The precipitate was collected by filtration again and washed with water to give 4-cyano-2-methoxypyridine (1.93 g, 72% yield) as a white solid. Mass spectrum (electrospray positive ion mode) m/z 135 [M + H]+.
References
[1] Journal of Medicinal Chemistry, 2008, vol. 51, # 21, p. 6631 - 6634
[2] Patent: WO2006/9889, 2006, A1. Location in patent: Page/Page column 54
[3] Patent: WO2006/33011, 2006, A1. Location in patent: Page/Page column 28
[4] Journal of Medicinal Chemistry, 2017, vol. 60, # 7, p. 2669 - 2684
[5] European Journal of Medicinal Chemistry, 1993, vol. 28, # 7-8, p. 601 - 608
