Synthesis
The general procedure for the synthesis of methyl 2-bromo-4-methylbenzoate from methanol and 2-bromo-4-methylbenzoic acid was as follows: concentrated sulfuric acid (4 mL) was slowly added to an anhydrous methanol (200 mL) solution of 2-bromo-4-methylbenzoic acid (10.0 g, 46.5 mmol). The reaction mixture was heated to reflux for 18 hours. After completion of the reaction, it was cooled to room temperature and the reaction mixture was concentrated. The residue was partitioned between water and ethyl acetate for extraction. After separating the organic and aqueous layers, the aqueous layer was then extracted with ethyl acetate (3 x 100 mL). All organic extracts were combined and washed sequentially with saturated sodium bicarbonate solution (2 x 50 mL) and brine, followed by drying with anhydrous magnesium sulfate. After filtration to remove the desiccant, the filtrate was concentrated to afford methyl 2-bromo-4-methylbenzoate (10.50 g, 99% yield), the product was a light amber colored oil. Mass spectrometry (MS) analysis showed m/z of 229.2 (M+H+).
References
[1] Patent: WO2008/124575, 2008, A1. Location in patent: Page/Page column 144
[2] Patent: WO2014/8197, 2014, A1. Location in patent: Page/Page column 163
[3] Patent: WO2015/95767, 2015, A1. Location in patent: Page/Page column 178
[4] Antimicrobial Agents and Chemotherapy, 2016, vol. 60, # 7, p. 3980 - 3987
[5] Patent: US2005/70584, 2005, A1. Location in patent: Page/Page column 23; 24
