Synthesis
General procedure for the synthesis of (2-bromo-5-methoxy-phenyl)methanol from 2-bromo-5-methoxybenzoic acid: 2-bromo-5-methoxybenzoic acid (2.25 g, 9.7 mmol) was dissolved in tetrahydrofuran (THF, 10 mL) and the solution was cooled to 0 °C. Under stirring, a tetrahydrofuran solution of 1 M borane (48 mL, 48 mmol) was slowly added, followed by gradual warming of the reaction mixture to room temperature. Upon completion of the reaction, the reaction mixture was slowly poured into a mixture of ice and saturated aqueous sodium bicarbonate solution. The aqueous phase was extracted with ethyl acetate and the organic layers were combined and washed sequentially with water and saturated aqueous sodium bicarbonate solution. The organic layer was dried with anhydrous sodium sulfate, filtered and concentrated in vacuum to give 2.1 g (100% yield) of the target product (2-bromo-5-methoxy-phenyl)methanol. Its nuclear magnetic resonance hydrogen spectrum (1H NMR, CDCl3) data were as follows: δ 7.42 (d, J = 8.8 Hz, 1H), 7.06 (d, J = 3.1 Hz, 1H), 6.72 (dd, J = 8.8, 3.1 Hz, 1H), 4.71 (s, 2H), 3.81 (s, 3H).
References
[1] Patent: WO2004/9578, 2004, A2. Location in patent: Page 31
[2] Journal of Organic Chemistry, 2005, vol. 70, # 2, p. 756 - 759
[3] European Journal of Medicinal Chemistry, 2015, vol. 94, p. 149 - 162
[4] Journal of Organic Chemistry, 1993, vol. 58, # 17, p. 4579 - 4583
[5] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 17, p. 4511 - 4514
