Synthesis
General procedure for the synthesis of methyl 2-(bromomethyl)-5-chlorobenzoate from methyl 2-methyl-5-chlorobenzoate: methyl 5-chloro-2-methylbenzoate (10.0 g, 54 mmol), N-bromosuccinimide (NBS, 10.6 g, 59.5 mmol), and azobisisobutyronitrile (AIBN, 200 mg) were dissolved in 1,2-dichloroethane ( 300 mL). The reaction mixture was irradiated and stirred for 2 h under photocatalytic conditions using [PHOTOLAMP]. Upon completion of the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with heptane/dichloromethane as eluent (gradient elution: 9:1, 4:1, 1:1) to afford 11.8 g of methyl 2-(bromomethyl)-5-chlorobenzoate (83% yield). The product was characterized by 1H NMR (300 MHz, CDCl3): δ 7.98 (d, J = 2.1 Hz, 1H), 7.49 (dd, J = 2.2, 8.2 Hz, 1H), 7.43 (d, J = 8.2 Hz, 1H), 4.93 (s, 2H), 3.97 (s, 3H).
References
[1] Patent: WO2004/18414, 2004, A2. Location in patent: Page 112
[2] Patent: WO2005/21508, 2005, A1. Location in patent: Page/Page column 148
[3] Israel Journal of Chemistry, 1971, vol. 9, p. 111 - 118
[4] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 5, p. 1628 - 1631
[5] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 1, p. 360 - 365
