Synthesis
14.6 g (0.1 mol) of 8-hydroxyquinoline, 16 mL of 32% aqueous hydrochloric acid and 16 mL (0.1 mol) of 37% aqueous formaldehyde were mixed at 0°C and passed through hydrogen chloride gas to react for 6 hours. After completion of the reaction, the mixture was allowed to stand at room temperature for 2 hours without stirring. The yellow solid produced by the reaction was collected by filtration, washed with 90% ethanol and dried under vacuum to afford 5-(chloromethyl)-8-quinolinol hydrochloride (19.0 g, 98% yield). The structure of the product was confirmed by 1H NMR (250 MHz, CDCl3): δ 5.32 (s, 2H), 7.53 (m, 1H), 7.85 (m, 2H), 8.12 (m, 1H), 9.12 (m, 1H), 9.28 (m, 1H).
References
[1] Journal of Medicinal Chemistry, 2014, vol. 57, # 24, p. 10455 - 10463
[2] Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 3, p. 773 - 783
[3] Patent: WO2012/20389, 2012, A1. Location in patent: Page/Page column 22
[4] Journal of Medicinal Chemistry, 2015, vol. 58, # 21, p. 8616 - 8637
[5] Journal of Molecular Liquids, 2016, vol. 219, p. 396 - 404
