Synthesis
Methyl 2-bromomethyl-5-methoxybenzoate (75, 5.0 g, 19.3 mmol) was used as raw material and dissolved in methanol in a pressure flask. To this solution was added ammonia/methanol solution (2M, 30 ml). The reaction mixture was stirred at 125°C for 2 hours. After completion of the reaction, the solvent and excess ammonia were removed by distillation under reduced pressure. The resulting residue was ground with hexane/ethyl acetate (1:2 v/v). The solid product was vacuum filtered and dried in air for 2 h to afford 5-methoxy-2,3-dihydroisoindol-1-one (2.51 g, 65% yield) as a light yellow solid. The filtrate was concentrated and purified by silica gel column chromatography (eluent ratio hexane/ethyl acetate/methanol 3:1:0.5) to give an additional 270 mg of the target compound. The overall yield of the combined product was 86%. Mass spectrum (electrospray ionization) m/z 164.1.
References
[1] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 1, p. 222 - 227
[2] Patent: WO2006/138549, 2006, A1. Location in patent: Page/Page column 73
[3] Patent: WO2009/14637, 2009, A2. Location in patent: Page/Page column 70-71
[4] Patent: WO2010/54279, 2010, A1. Location in patent: Page/Page column 100-101
[5] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 24, p. 7283 - 7287
