Synthesis
Step 1. Synthesis of methyl 4-fluoro-2-methylbenzoate: 4-fluoro-2-methylbenzoic acid (50 g, 324.38 mmol) was mixed with thionyl chloride (SOCl2, 77 g, 648.76 mmol) in methanol (200 mL), and heated to reflux for 3 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to afford methyl 4-fluoro-2-methylbenzoate as a brown oil (52 g, 95% yield). The product was characterized by 1H-NMR (300 MHz, CDCl3): δ 7.92-7.98 (m, 1H), 6.88-6.95 (m, 2H), 3.90 (s, 3H), 2.61 (s, 3H).
References
[1] Patent: US2012/277224, 2012, A1. Location in patent: Page/Page column 60
[2] Patent: WO2010/69966, 2010, A1. Location in patent: Page/Page column 78-79
[3] Patent: US6342504, 2002, B1. Location in patent: Page column 119
[4] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 24, p. 6707 - 6713
[5] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 5, p. 1628 - 1631
