Synthesis
General procedure for the synthesis of 4-bromo-3,5-dimethoxybenzenemethanol from methyl 4-bromo-3,5-dimethoxybenzoate: a solution of LiAlH4 (4.43 g, 0.12 mol) in freshly distilled anhydrous THF (45 mL) was added slowly and dropwise to a stirring 4-bromo-3,5-dimethoxybenzoic acid methyl ester (5.48 g, 0.02 mol) in a THF (80 mL) solution. The reaction mixture was stirred at 0 °C for 15 min, followed by recovery to room temperature and continued stirring for 8 h. The reaction was completed with the use of saturated chlorine chloride. Upon completion of the reaction, the reaction was quenched with saturated ammonium chloride solution (140 mL), stirred for 1 h, acidified with dilute hydrochloric acid and extracted with ethyl acetate (3 x 25 mL). The organic phases were combined, the solvents were evaporated after drying, and the resulting crude product was recrystallized from petroleum ether to give 4-bromo-3,5-dimethoxybenzyl alcohol as colorless prismatic crystals (4.42 g, 90% yield). The product was characterized as follows: Rf = 0.35; melting point 96-97 °C (literature value 34a, 100-102 °C); IR (KBr) νmax: 3362 (O-H), 3024 (C=C-H), 1574 (C=C) cm-1; 1H NMR (300 MHz, CDCl3) δ 6.50 (2H, s, H-2, H-6), and 4.57 (2H, s, ArCH2), 3.75 (6H, s, OCH3), 2.48 (1H, s, OH) ppm; 13C NMR (CDCl3) δ: 158.3 (C-3,5), 142.7 (C-1), 121.7 (C-4), 112.5 (C-2,6), 63.3 (OCH3), 62.0 ( OCH3), 42.1 (CH2) ppm. elemental analysis (C9H11BrO3) Calculated: C, 43.70; H, 4.48; Measured: C, 43.70; H, 4.24. GC-MS m/z 245.9, 247.9.
References
[1] Tetrahedron, 2014, vol. 70, # 7, p. 1401 - 1407
[2] Patent: US2005/59733, 2005, A1
[3] European Journal of Organic Chemistry, 2002, # 19, p. 3294 - 3303
[4] Journal of Medicinal Chemistry, 1977, vol. 20, # 2, p. 299 - 301
[5] Patent: WO2003/72536, 2003, A1. Location in patent: Page/Page column 26-27
