Uses
4,4-Difluorocyclohexanecarboxylic Acid Ethyl Ester is used as a reactant in the preparation of antiretroviral drug Maraviroc (M193000), which is CCR-5 receptor antagonist used for the treatment of HIV.
Synthesis
General procedure for the synthesis of ethyl 4,4-difluorocyclohexanecarboxylate from ethyl cyclohexanonecarboxylate: ethyl 4-oxocyclohexanecarboxylate (5 g, 29 mmol) of the compound 4-oxocyclohexanecarboxylic acid (5 g, 29 mmol) was slowly added dropwise by dissolving DAST (7.7 mL) in 75 mL CCl4 at 0 °C. After the dropwise addition was completed, the reaction mixture was stirred at room temperature for 16 hours. Upon completion of the reaction, the reaction was quenched by slow addition of water, the organic phase was separated, washed with water and dried with Na2SO4. Finally, purification by distillation gave ethyl 4,4-difluorocyclohexanecarboxylate as a colorless oil (4.2 g, 71% yield).
References
[1] Patent: WO2013/13188, 2013, A1. Location in patent: Paragraph 00312
[2] Patent: US9416132, 2016, B2. Location in patent: Page/Page column 134
[3] Patent: US2014/275080, 2014, A1. Location in patent: Paragraph 0427
[4] Patent: WO2018/213150, 2018, A1. Location in patent: Page/Page column 20; 21; 28
[5] Patent: US5968923, 1999, A
