Synthesis
General procedure for the synthesis of 3,3-difluorocyclobutanecarboxylic acid from benzyl ester of 3,3-difluorocyclobutanecarboxylate: benzyl ester of 3,3-difluorocyclobutanecarboxylic acid (0.84 g, 3.72 mmol) was dissolved in ethanol (40 mL), and about 0.02 g of palladium/activated carbon catalyst was added. The reaction mixture was stirred at room temperature for 12 hours in a hydrogen atmosphere. Upon completion of the reaction, the catalyst was removed by filtration through a diatomaceous earth pad. The filtrate was concentrated and dried under vacuum to afford the target product 3,3-difluorocyclobutanecarboxylic acid (0.46 g, 90% yield). The structure of the product was confirmed by 1H NMR (400 MHz, CDCl3): δ 3.16-2.55 (m, 5H).
References
[1] Patent: WO2013/107405, 2013, A1. Location in patent: Page/Page column 42
[2] Patent: US2015/87600, 2015, A1. Location in patent: Page/Page column
[3] Patent: EP3290418, 2018, A1. Location in patent: Paragraph 0172; 0181
[4] Patent: US9273058, 2016, B2. Location in patent: Page/Page column 337; 338
[5] Patent: WO2007/47625, 2007, A2. Location in patent: Page/Page column 24
