Synthesis
(1a) Synthesis of 3-bromo-5-methoxyphenol: Commercially available 1-bromo-3,5-dimethoxybenzene (18.74 g, 86.3 mmol) was dissolved in 1-methyl-2-pyrrolidinone (100 mL), and sodium methanethiol (6.74 g, 96.2 mmol) was added. The reaction mixture was stirred at 100 °C for 3 h under nitrogen protection. After completion of the reaction, the reaction solution was cooled to room temperature, acidified by adding 1N hydrochloric acid (200 mL) and extracted with ether (500 mL). The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was removed by concentration under reduced pressure and the resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane, 20%-25% gradient) to afford the target compound 3-bromo-5-methoxyphenol (15.03 g, 86% yield) as a white solid.1H-NMR (CDCl3, 400 MHz) δ: 3.77 (3H, s), 4.82 (1H, s), 6.33 (1H, s), 6.33 (1H, s). 6.33 (1H, t, J = 2.4 Hz), 6.61 (1H, t, J = 2.0 Hz), 6.66 (1H, t, J = 2.0 Hz).
References
[1] Patent: EP2239253, 2010, A1. Location in patent: Page/Page column 44
[2] European Journal of Organic Chemistry, 2016, vol. 2016, # 3, p. 426 - 429
[3] Tetrahedron Letters, 2018, vol. 59, # 17, p. 1670 - 1673
[4] Patent: WO2007/34325, 2007, A1. Location in patent: Page/Page column 68
[5] Patent: US2011/105562, 2011, A1. Location in patent: Page/Page column 18
