Synthesis
5-Methyl-2-nitrobenzoic acid (8 g, 44.198 mmol) was dissolved in methanol (80 mL) and the solution was cooled to 0°C. Sulfuric acid (5 mL) was added slowly and dropwise with stirring. Subsequently, the reaction mixture was heated to 90 °C and stirred continuously at this temperature for 16 hours. The progress of the reaction was monitored by thin layer chromatography (TLC, unfolding agent 50% ethyl acetate/hexane). After completion of the reaction, excess methanol was removed by distillation under reduced pressure. The residue was poured into water (150 mL) and extracted with ethyl acetate (150 mL x 2). The organic phases were combined and washed sequentially with saturated sodium bicarbonate solution (50 mL x 2) and brine (20 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to afford methyl 5-methyl-2-nitrobenzoate (yield: 8 g, 93%). The structure of the product was confirmed by 1H NMR (400 MHz, CDCl3): δ 7.86-7.84 (d, 1H, J = 8Hz), 7.48 (s, 1H), 7.40-7.38 (d, 1H, J = 8Hz), 3.91 (s, 3H), 3.47 (s, 3H).
References
[1] Journal of Heterocyclic Chemistry, 1984, vol. 21, p. 1807 - 1816
[2] Patent: WO2015/38417, 2015, A1. Location in patent: Paragraph 151
[3] Bulletin of the Korean Chemical Society, 2011, vol. 32, # 12, p. 4309 - 4315
[4] Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 7, p. 2209 - 2224
[5] Chemische Berichte, 1909, vol. 42, p. 433
