Synthesis
General procedure for the synthesis of methyl 2-bromomethyl-3-methoxybenzoate from methyl 3-methoxy-2-methylbenzoate: to a solution of CHCl3 (2-5 mL/mmol) or CCl4 (5 mL/mmol) containing methyl 3-methoxy-2-methylbenzoate (1.00 eq.), N-bromosuccinimide (NBS, 1.10- 2.20 eq.) and azobisisobutyronitrile (AIBN, 0.02-0.04 eq.). The reaction mixture was heated to reflux for 2-22 hours and subsequently cooled to room temperature. Upon completion of the reaction, the solvent is removed by evaporation under reduced pressure if CHCl3 is used as solvent, or by distillation if CCl4 is used, to give the target product methyl 2-bromomethyl-3-methoxybenzoate. Precautions: CHCl3 and CCl4 are highly toxic and carcinogenic, protective gloves should be worn and the operation should be carried out in a fume hood.
References
[1] Tetrahedron, 2018, vol. 74, # 2, p. 224 - 239
[2] Journal of Organic Chemistry, 1980, vol. 45, # 1, p. 12 - 15
[3] Patent: WO2004/26875, 2004, A1. Location in patent: Page 38
[4] Patent: US2004/106791, 2004, A1. Location in patent: Page 9
[5] Chinese Chemical Letters, 2012, vol. 23, # 1, p. 9 - 12
