General procedure for the synthesis of 4-nitro-isoindolin-1-one from methyl 2-(bromomethyl)-3-nitrobenzoate: methyl 2-(bromomethyl)-3-nitrobenzoate (20 g) was dissolved in methanol (200 ml) and stirred at room temperature under ammonia atmosphere for 30 min, followed by keeping the reaction for 2 hours. After completion of the reaction, the mixture was crystallized in an ice bath for 2 h. The crystals were collected by filtration and dried to give 11.7 g of light yellow crystals in 90% yield. The melting point was 235.4~236.7 °C. 1H-NMR (300 MHz, DMSO-d6) δ: 4.78 (s, 2H), 7.79 (t, 1H), 8.10 (d, 1H), 8.41 (d, 1H), 8.90 (s, 1H). 1H-NMR (300 MHz, DMSO-d6/EtOH) δ: 4.76 (s 2H), 7.77 (t, 1H), 8.08 (d, 1H), 8.39 (d, 1H).FAB-MS (M+1): 179.Elemental analysis: theoretical value (%): C 53.94, H 3.39, N 15.72; measured value (%): C 54.08, H 3.49, N 15.81.HPLC analytical conditions: chromatographic column: Phenomenex Luna 5μ C18 (250mm×4.6mm); Flow rate: 1.0ml/min; Detection wavelength: 230nm; Mobile phase: Acetonitrile/0.1% Phosphate buffer=30/70 (v/v); Retention time of the target product: 5.810 min; Purity: 99.59%.
