Synthesis
Step A. Synthesis of methyl 4-bromo-3-hydroxybenzoate: To a solution of methanol (100 mL) containing 4-bromo-3-hydroxybenzoic acid (30 mmol) was slowly added concentrated sulfuric acid (2.6 mL). The reaction mixture was heated to reflux for 5 hours. Upon completion of the reaction, the mixture was cooled to 0 °C, followed by the slow addition of saturated aqueous sodium carbonate to adjust the pH to 7. The reaction solution was concentrated to one-third of the original volume and diluted with an appropriate amount of water. Extraction was carried out with ethyl acetate and the organic phases were combined. The organic phase was washed with water and saturated saline in turn and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give a white solid product, methyl 4-bromo-3-hydroxybenzoate, 6.15 g (89% yield) with a melting point of 205 °C (literature value: 130-132 °C).
References
[1] Chemical Communications, 2013, vol. 49, # 10, p. 990 - 992
[2] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 16, p. 4863 - 4867
[3] Journal of Medicinal Chemistry, 2007, vol. 50, # 15, p. 3540 - 3560
[4] Patent: US2006/199806, 2006, A1. Location in patent: Page/Page column 23
[5] Patent: WO2005/115996, 2005, A1. Location in patent: Page/Page column 66
