Synthesis
Using 5-methylthiophene-2-carbonitrile (9.9 g, 80.5 mmol) as starting material, benzoyl peroxide (0.23 g, 0.95 mmol) and N-bromosuccinimide (15 g, 84.3 mmol) were added in carbon tetrachloride (200 mL), and the reaction was heated and refluxed for 6 hours. Upon completion of the reaction, the resulting suspension was filtered and the filtrate was diluted with dichloromethane (400 mL) and subsequently washed with saturated sodium bicarbonate solution and dried with magnesium sulfate. The dried solution was concentrated under vacuum to give the crude product. The crude product was purified by column chromatography (eluent: ethyl acetate/hexane, 1:4) to afford 5-bromomethylthiophene-2-carbonitrile as a yellow oil (14.0 g, 86% yield). The structure of the product was confirmed by 1H NMR (CDCl3): δ 7.50 (d, 1H), 7.13 (d, 1H), 4.68 (s, 2H).FAB MS showed the molecular ion peak as 203 [M + 1]+.
References
[1] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 5, p. 743 - 748
[2] Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 13, p. 1683 - 1686
[3] Journal of Medicinal Chemistry, 2003, vol. 46, # 17, p. 3612 - 3622
[4] Patent: EP1140918, 2004, B1. Location in patent: Page 14
[5] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 7, p. 1017 - 1022
