The general procedure for the synthesis of methyl 2-amino-3-chlorobenzoate from methyl 2-nitro-3-chlorobenzoate was as follows: iron powder (1.94 g, 34.8 mmol) was added to an ethanol/acetic acid (100 mL/100 mL) solution of methyl 3-chloro-2-nitrobenzoate (2.5 g, 11.6 mmol) at room temperature. Subsequently, the suspension was refluxed for 2 h under nitrogen protection. After completion of the reaction, it was cooled to room temperature and the solvent was partially removed by rotary evaporator. The resulting residue was partitioned between water/ethyl acetate (200 mL/300 mL). The organic phase was separated and washed sequentially with 1N aqueous sodium hydroxide (50 mL), brine (50 mL), dried over anhydrous magnesium sulfate, and concentrated by rotary evaporator to afford the target product, methyl 2-amino-3-chlorobenzoate, as a tan oily substance (1.7 g, 79% yield), which was converted to a waxy solid upon standing. The crude product was pure enough to be used in subsequent steps without further purification. The product was confirmed by 1H NMR (400 MHz, CDCl3): δ 3.86 (s, 3H), 6.25 (s, 2H), 6.57 (t, J = 7.93 Hz, 1H), 7.39 (dd, J = 7.81, 1.51 Hz, 1H), 7.79 (dd, J = 8.06, 1.51 Hz, 1H). Mass spectrometry analysis showed a molecular ion peak of 185.95 (MH+) and a calculated value of 185.02 for C8H8ClNO2.
