Synthesis
The general procedure for the synthesis of methyl 2-bromomethyl-4-methoxybenzoate from methyl 4-methoxy-2-methylbenzoate was as follows: N-bromosuccinimide (1.1 g, 6.2 mmol) and a catalytic amount of methyl 4-methoxy-2-methylbenzoate (1 g, 5.6 mmol) were pre-dissolved in carbon tetrachloride (5 mL), which was subsequently added dropwise to a solution containing 25 mL of carbon tetrachloride. After addition of benzoyl peroxide, the reaction mixture was refluxed for 2 hours. After completion of the reaction, it was cooled to room temperature and the mixture was poured into ice water. The aqueous phase was extracted with dichloromethane (3×), and the combined organic phases were dried over magnesium sulfate, filtered, and concentrated under vacuum to afford 2.1 g of the target product, methyl 2-bromomethyl-4-methoxybenzoate, as a light yellow solid in about 100% yield. Mass spectrometry analysis showed [M + H+] m/z 260.
References
[1] Patent: WO2011/85261, 2011, A1. Location in patent: Page/Page column 36
[2] Patent: WO2011/85128, 2011, A1. Location in patent: Page/Page column 56
[3] Journal of Medicinal Chemistry, 1987, vol. 30, # 10, p. 1798 - 1806
[4] Patent: US2008/249101, 2008, A1. Location in patent: Page/Page column 40
[5] Patent: WO2008/20306, 2008, A2. Location in patent: Page/Page column 35
