Synthesis
Dissolve 3-bromo-2-methoxybenzoic acid (1-4 g) in methanol (25-75 mL) and concentrate. Concentrated sulfuric acid (2-6 mL) was added dropwise with stirring. The reaction mixture was heated to reflux and stirred for 24 hours. Upon completion of the reaction, the mixture was quenched in saturated aqueous sodium bicarbonate (100-200 mL) and the pH was adjusted to neutral to basic. Subsequently, the aqueous phase was extracted with dichloromethane (4 x 50 mL). The organic phases were combined, washed with saturated aqueous sodium chloride solution (25-50 mL), dried over anhydrous sodium sulfate and filtered. After concentration, methyl 3-bromo-2-methoxybenzoate was obtained in high yield and purity. Specific example: 3-bromo-2-methoxybenzoic acid (1.00 g, 4.33 mmol) was used as raw material and prepared according to the above method to obtain 1.07 g (4.33 mmol, 100%) of methyl 3-bromo-2-methoxybenzoate, the product was a transparent oil, with an HPLC purity of 99%, and a retention time (t R) of 21.5 min.1H NMR ( 600 MHz, DMSO-d6) δ: 7.88-7.84 (m, 1H), 7.73-7.70 (m, 1H), 7.18 (t, J = 7.8 Hz, 1H), 3.86 (s, 3H), 3.81 (s, 3H); 13C NMR (150 MHz, DMSO-d6) δ: 165.1, 155.7 137.0, 130.3, 126.8, 125.6, 118.1, 61.8, 51.4; HRMS (APCI/ASAP, m/z): 244.9813 (calculated value of C9H1079BrO3, 244.9813, [M + H]+).1H NMR data are in agreement with the literature reports.
References
[1] European Journal of Medicinal Chemistry, 2016, vol. 107, p. 255 - 274
[2] Bioorganic and Medicinal Chemistry Letters, 1999, vol. 9, # 24, p. 3447 - 3452
[3] Patent: WO2009/152082, 2009, A1. Location in patent: Page/Page column 198
[4] European Journal of Medicinal Chemistry, 2014, vol. 90, p. 526 - 536
[5] Patent: US2008/194650, 2008, A1. Location in patent: Page/Page column 22-23
