Synthesis
General procedure for the synthesis of methyl 3-fluoro-4-formylbenzoate (compound 14D) from 3-fluoro-4-formylbenzoic acid (compound 14C, 0.25 g, 1.49 mmol) and iodomethane: Compound 14C was dissolved in DMF (4.5 mL), and sodium hydride (60% oil dispersion, 0.069 g, 1.73 mmol) was added. The reaction mixture was stirred under nitrogen protection for 30 min, followed by the addition of iodomethane (0.11 mL, 1.74 mmol). The reaction was stirred continuously at room temperature for about 15 hours. Upon completion of the reaction, the mixture was poured into 1N HCl solution and extracted several times with EtOAc. The organic phases were combined, washed with saturated brine, dried over anhydrous MgSO4, filtered and concentrated under reduced pressure to give compound 14D as a wet residue, which solidified to a white solid after standing (0.23 g, 85% yield).
References
[1] Patent: WO2008/130584, 2008, A1. Location in patent: Page/Page column 144-145
[2] Patent: WO2013/74641, 2013, A1. Location in patent: Paragraph 00382
[3] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 17, p. 4804 - 4807
[4] Patent: WO2004/89916, 2004, A1. Location in patent: Page 22-23
[5] Journal of Medicinal Chemistry, 2009, vol. 52, # 19, p. 5950 - 5966
