General procedure for the synthesis of 2-methyl-5-nitrobenzoic acid from methyl 2-methyl-5-nitrobenzoate: To a solution of methyl 2-methyl-5-nitrobenzoate (75.0 g, 0.46 mol) in tetrahydrofuran (THF, 500 mL) was added a 1N aqueous solution of lithium hydroxide (LiOH) (1 L, 0.92 mol). The reaction mixture was stirred at 30 °C for 4 hours. The progress of the reaction was monitored by thin layer chromatography (TLC, unfolding reagent ratio of petroleum ether: ethyl acetate = 10:1), and after confirming the completion of the reaction, the mixture was concentrated under reduced pressure. The residue was extracted with ethyl acetate (200 mL x 2). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and subsequently concentrated under reduced pressure to afford 2-methyl-5-nitrobenzoic acid (67 g, 98% yield) as a brown solid, which could be used in subsequent steps without further purification. The structure of the product was confirmed by 1H NMR (400 MHz, CDCl3): δ 8.93 (s, 1H), 8.30-8.32 (d, J=8.0 Hz, 1H), 7.48-7.50 (d, J=8.0 Hz, 1H), 2.79 (s, 3H).
