Synthesis
GENERAL STEPS: Sodium methanolate (5 M methanol solution, 3.5 mL, 17.6 mmol) and methyl mercaptoacetate (1.8 mL, 20.1 mmol) were added sequentially to 3-methoxy-2-phenylacrylonitrile (2 g, 12.6 mmol). The reaction mixture was stirred and refluxed at 65 °C overnight. After completion of the reaction, the mixture was filtered using diatomaceous earth and the filter cake was washed with dichloromethane. The crude product was purified by column chromatography (silica gel, n-hexane: ethyl acetate = 5:1) to afford the white solid product methyl 3-amino-4-phenylthiophene-2-carboxylate (1.5 g, 6.6 mmol, 52% yield in two steps). The structure of the product was confirmed by 1H NMR (300 MHz, CDCl3): δ 7.49-7.39 (m, 5H), 7.25 (s, 1H), 5.64 (br, 2H), 3.88 (s, 3H).
References
[1] Bulletin of the Korean Chemical Society, 2015, vol. 36, # 5, p. 1439 - 1451
[2] Patent: US2014/228565, 2014, A1. Location in patent: Paragraph 0197; 0198
[3] European Journal of Medicinal Chemistry, 2014, vol. 85, p. 629 - 637
