Synthesis
Step A: Thionyl chloride (2.8 mL, 39.0 mmol) was added slowly and dropwise to a stirred solution of 2-fluoro-3-methylbenzoic acid (4.0 g, 26.0 mmol) in anhydrous methanol (52 mL) at 0 °C. The reaction mixture was stirred overnight under reflux conditions. Upon completion of the reaction, the mixture was diluted with methanol and the excess thionyl chloride was subsequently removed by concentration under reduced pressure. The residue was dissolved in ethyl acetate, the organic layer was washed with saturated aqueous sodium bicarbonate, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to afford methyl 2-fluoro-3-methylbenzoate (3.6 g, 83% yield) as a clear oil. The product could be used in subsequent steps without further purification.1H NMR (500 MHz, CDCl3) δ 7.75-7.72 (m, 1H), 7.38-7.35 (m, 1H), 7.26-7.06 (m, 1H), 3.91 (s, 3H), 2.31 (s, 3H).
References
[1] Patent: WO2011/8572, 2011, A2. Location in patent: Page/Page column 62
[2] Patent: WO2005/18557, 2005, A2. Location in patent: Page/Page column 304
