Synthesis
General procedure for the synthesis of methyl 2-methyl-4-nitrobenzoate from methanol and 2-methyl-4-nitrobenzoic acid:
1. SOCl was added slowly and dropwise to a methanolic solution of 2-methyl-4-nitrobenzoic acid (3 g, 16.5 mmol).
2. the reaction mixture was stirred continuously at 70 °C for 18 hours.
3. After completion of the reaction, the solvent was removed by evaporation and the residue was diluted with ether.
4. The ether phase was washed sequentially with water and 1N NaOH solution. 5.
5. The organic phase was dried with anhydrous NaSO, filtered and the solvent was evaporated to give methyl 2-methyl-4-nitrobenzoate as a dark yellow solid (3.25 g, quantitative yield).
NMR data: 1H NMR (300 MHz, CDCl) δ: 7.95 (m, 3H), 3.86 (s, 3H), 2.59 (s, 3H).
References
[1] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 3, p. 942 - 945
[2] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 3, p. 946 - 949
[3] Patent: WO2009/47240, 2009, A1. Location in patent: Page/Page column 28
[4] Journal of Medicinal Chemistry, 1999, vol. 42, # 18, p. 3510 - 3519
[5] Patent: CN103804358, 2016, B. Location in patent: Paragraph 0117
