Synthesis
Thionyl chloride (1.3 mL, 17.8 mmol) was added slowly and dropwise to a stirred mixed solution of 4-methoxy-2-methylbenzoic acid (1.0 g, 6 mmol) and methanol (50 mL) at room temperature and under nitrogen protection. The reaction mixture was heated to reflux and maintained for 3 hours. Upon completion of the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure to give a light yellow crude product. The crude product was purified by silica gel column chromatography with the eluent of petroleum ether: ethyl acetate (9:1, v/v) to afford methyl 4-methoxy-2-methylbenzoate (1.11 g, 100% yield) in colorless liquid form. The product was characterized by 1H NMR (400 MHz, DMSO-d6) and ESI-MS: 1H NMR δ 7.81 (d, J = 9 Hz, 1H), 6.86 (d, J = 3 Hz, 1H), 6.83 (dd, J = 9, 3 Hz, 1H), 3.78 (s, 3H), 3.75 (s, 3H), 2.49 (s, 3H); ESI -MS m/z 181 ([M+H]+).
References
[1] Patent: WO2009/5998, 2009, A1. Location in patent: Page/Page column 214
[2] Patent: WO2004/14856, 2004, A1. Location in patent: Page 9; 14
[3] Patent: WO2008/20306, 2008, A2. Location in patent: Page/Page column 35
[4] Journal of Medicinal Chemistry, 2013, vol. 56, # 21, p. 8561 - 8578
[5] Tetrahedron, 2018, vol. 74, # 2, p. 224 - 239
