Synthesis
General procedure for the synthesis of (2-amino-4-chlorophenyl)methanol from 4-chloro-2-nitrobenzenemethanol: 4-chloro-2-nitrobenzenemethanol (1 g, 5.33 mmol, ALDRICH) and platinum(IV) oxide (100 mg, 0.44 mmol) were suspended in ethanol (100 mL) and hydrogenated for 1 hr at room temperature and 1300 mbar hydrogen pressure. . After completion of the reaction, the suspension was filtered, the filter cake was washed with ethanol, and the filtrates were combined and concentrated to dryness to give the crude product (2-amino-4-chlorophenyl)methanol as a light orange solid. The crude product was purified by rapid chromatography on silica gel, the eluent being a gradient of dichloromethane solution of 0 to 3% methanol. The target fraction was collected and the solvent was evaporated to dryness to give the pure product (2-amino-4-chlorophenyl)methanol (0.650 g, 77% yield) as a light orange solid. NMR hydrogen spectrum (DMSO-d6) data: δ 4.34 (d, 2H), 5.06 (t, 1H), 5.20 (s, 2H), 6.51 (dd, 1H), 6.64 (d, 1H), 7.05 (d, 1H).
References
[1] Angewandte Chemie - International Edition, 2017, vol. 56, # 35, p. 10573 - 10576
[2] Angew. Chem., 2017, vol. 129, # 35, p. 10709 - 10712,4
[3] Synlett, 2017, vol. 28, # 14, p. 1724 - 1728
[4] Patent: WO2008/104754, 2008, A1. Location in patent: Page/Page column 178-179
[5] Journal of Medicinal Chemistry, 1993, vol. 36, # 22, p. 3397 - 3408
