Synthesis
The reaction was carried out with methyl 5-hydroxy-4-methoxy-2-nitrobenzoate (15.4 g, 68 mmol) and benzyl bromide (9.7 mL, 82 mmol) in the presence of cesium carbonate (44 g, 136 mmol) with stirring at room temperature in DMSO (200 mL) for 24 hours. After completion of the reaction, the reaction mixture was diluted with ethyl acetate (~2 L) and n-butanol (~100 mL). The organic layer was washed sequentially with water and brine, dried with magnesium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (eluent ratio from 1:5 to 2:1 ethyl acetate-hexane) to afford methyl 2-nitro-4-methoxy-5-benzyloxybenzoate 20.2 g in 94% yield; MS (AP/CI): 286.1 (M + H)+.
References
[1] Patent: WO2008/20302, 2008, A2. Location in patent: Page/Page column 28
[2] Journal of Medicinal Chemistry, 2011, vol. 54, # 13, p. 4536 - 4547
