Synthesis
GENERAL METHOD: A catalytic amount of concentrated H2SO4 (0.1 mmol) was added to a methanol (50 mL) solution of 2,6-difluorobenzoic acid (1.0 mmol) and the mixture was heated to reflux for 6 hours. Upon completion of the reaction, the reaction mixture was cooled to room temperature. Subsequently, saturated NaHCO3 solution (50 mL) was added to the reaction mixture to neutralize the acidic conditions, and then the product was extracted with ethyl acetate (2 x 50 mL). The organic phases were combined, dried with anhydrous Na2SO4, filtered and concentrated under reduced pressure to give pure methyl 2,6-difluorobenzoate.
References
[1] Organic Process Research and Development, 2016, vol. 20, # 2, p. 233 - 241
[2] Medicinal Chemistry Research, 2016, vol. 25, # 4, p. 627 - 643
[3] Patent: WO2011/59610, 2011, A1. Location in patent: Page/Page column 101-102
[4] Patent: WO2013/71865, 2013, A1. Location in patent: Page/Page column 25
[5] Patent: CN103102349, 2017, B. Location in patent: Paragraph 0147-0149
