17100-58-2

Step a: 2-methyl-4-bromobenzoic acid (11.1 g, 51.6 mmol) was dissolved in anhydrous THF (11.2 mL). The solution was cooled to 0-5 °C and 1 M of BH3-THF solution (103 mL) was added slowly. The reaction mixture was stirred at room temperature for 3 hours. Upon completion of the reaction, the reaction was quenched by careful addition of cold water (20 mL) and subsequently washed with saturated NaHCO3 solution (120 mL). The aqueous phase was extracted with ether (3 x 300 mL) and the combined organic phases were washed with brine (200 mL), dried with anhydrous MgSO4 and concentrated in vacuum. The resulting crude product was purified by fast column chromatography with a gradient ratio of hexane/EtOAc (from 95:5 to 70:30) as eluent to afford the target product (4-bromo-2-methylphenyl)methanol (10.4 g, 100% yield) as a colorless transparent oil.1H NMR (300 MHz, CDCl3): δ 7.36-7.30 (2H, m), δ 7.25-7.21 (1H, m), 4.65 (2H, s), 2.32 (3H, s).

[1] Journal of Medicinal Chemistry, 1984, vol. 27, # 11, p. 1516 - 1531
[2] Patent: WO2008/18827, 2008, A1. Location in patent: Page/Page column 61
[3] Patent: WO2014/78608, 2014, A1. Location in patent: Paragraph 00280
[4] Patent: WO2015/171757, 2015, A1. Location in patent: Page/Page column 55
[5] Patent: US2014/100179, 2014, A1. Location in patent: Paragraph 0020; 0022