Synthesis
GENERAL STEPS: 3-Bromo-2-hydroxybenzaldehyde (5.0 g, 24.87 mmol) was dissolved in acetone (200 mL) and iodomethane (5.3 g, 37.34 mmol) and potassium carbonate (5.2 g, 37.63 mmol) were added sequentially. The reaction mixture was heated to 60 °C and stirred for 2 hours. After completion of the reaction, the mixture was cooled to room temperature and filtered to remove insoluble solids. The filtrate was concentrated to dryness by rotary evaporation and the resulting residue was redissolved in ethyl acetate. The organic phase was washed with saturated aqueous sodium bicarbonate and subsequently dried over anhydrous magnesium sulfate. After filtration to remove the desiccant, the filtrate was concentrated to give the crude product. The crude product was purified by silica gel column chromatography using 50% ethyl acetate in hexane solution as eluent. The eluate containing the target product was collected and concentrated to give 3-bromo-2-methoxybenzaldehyde (2.0 g, 93% yield) as a colorless slurry. Mass spectrometry analysis showed m/z 215.0 ([M+H]+); the high performance liquid chromatography retention time (HPLC rt) was 13.8 min [a].
References
[1] Patent: WO2013/10904, 2013, A1. Location in patent: Page/Page column 65
[2] Journal of Medicinal Chemistry, 2002, vol. 45, # 17, p. 3573 - 3575
[3] Patent: WO2011/33265, 2011, A1. Location in patent: Page/Page column 93-94
[4] Patent: WO2009/76602, 2009, A1. Location in patent: Page/Page column 161-162
[5] Synthesis (Germany), 2018, vol. 50, # 13, p. 2516 - 2522
