Step 1: Synthesis of 2-amino-3-(methoxycarbonyl)benzoic acid
Methyl 2,3-dioxo dihydroindole-7-carboxylate (1 eq.) was dissolved in methanol (0.4 M) and hydrogen chloride gas was passed into the solution at 0 °C with continuous stirring of the reaction mixture for 2 hours. After completion of the reaction, the solvent was removed by evaporation and the resulting residue was diluted with chloroform, washed sequentially with saturated aqueous sodium bicarbonate and brine, and the organic phase was dried over anhydrous sodium sulfate and then concentrated to give the crude product (MS (ES+) m/z 206 (M+H)+).
The above crude product was dissolved in 10% aqueous hydrogen peroxide solution, prepared as 0.2 M. An equal volume of 2.5% aqueous sodium hydroxide solution was added and the reaction was stirred for 15 min at room temperature. At the end of the reaction, the reaction mixture was acidified with concentrated hydrochloric acid, the precipitate precipitated was collected by filtration and washed with water to obtain monomethyl 2-aminoisophthalate in 88% yield as a white powder.
Product characterization data: 1H NMR (400MHz, DMSO-d6, 300K) δ 3.82 (s, 3H), 6.60 (t, 1H, J=7.4Hz), 8.04 (m, 3H), 12.94 (bs, 1H); MS (ES+) m/z 196 (M+H)+.
