Synthesis
General procedure for the synthesis of 2-(4,4-difluorocyclohexyl)acetic acid from ethyl 2-(4,4-difluorocyclohexyl)acetate: ethyl 2-(4,4-difluorocyclohexyl)acetate (3.2 g, 15.5 mmol) was dissolved in methanol (5 mL), lithium hydroxide (559 mg, 23.3 mmol) was added, and the reaction was stirred at room temperature overnight. Upon completion of the reaction, the pH of the reaction mixture was adjusted to 4 with 3N hydrochloric acid and then extracted with dichloromethane. The organic phases were combined, dried with anhydrous sodium sulfate and concentrated under reduced pressure to give 2-(4,4-difluorocyclohexyl)acetic acid (3 g, 100%) as a brown oil.
References
[1] Patent: US2006/264489, 2006, A1. Location in patent: Page/Page column 78
[2] Patent: US2013/183269, 2013, A1. Location in patent: Paragraph 1216; 1217
[3] Patent: US2015/23913, 2015, A1. Location in patent: Paragraph 1461-1462
[4] Patent: WO2015/5901, 2015, A1. Location in patent: Page/Page column 517; 518
[5] Patent: WO2006/122200, 2006, A1. Location in patent: Page/Page column 53
