Synthesis
Bromination reaction: Methyl 3-fluoro-4-methylbenzoate (18.3 mmol) was dissolved with N-bromosuccinimide (NBS, 3.9 g, 22 mmol) in carbon tetrachloride (40 mL), and benzoyl peroxide (0.55 g, 1.7 mmol) containing 25% water was added as initiator. The reaction mixture was stirred well and heated to reflux for 6 hours. Upon completion of the reaction, the solvent was removed by evaporation and the residue was treated with an aqueous solution of potassium carbonate (K2CO3) followed by extraction of the product with ethyl acetate (EtOAc). After treatment, methyl 3-fluoro-4-(bromomethyl)benzoate was obtained as a light yellow solid in a yield of 5.9 g. The product was analyzed by electrospray ionization mass spectrometry (ESI-MS), which showed the [M + H]+ peak as 247 Da.
References
[1] Patent: WO2014/102376, 2014, A1. Location in patent: Page/Page column 45
[2] Patent: WO2014/102377, 2014, A1. Location in patent: Page/Page column 49-50
[3] Journal of Medicinal Chemistry, 2015, vol. 58, # 15, p. 6058 - 6080
[4] Synlett, 2014, vol. 25, # 17, p. 2485 - 2487
[5] Patent: US2006/14945, 2006, A1. Location in patent: Page/Page column 60
