Chemical Properties
4,4-Difluorocyclohexanecarboxylic acid is White Solid
Uses
4,4-Difluorocyclohexanecarboxylic acid is a di-substituted cyclohexane carboxylic acids used in the synthesis of macrolide antibiotics.
Synthesis
The general procedure for the synthesis of 4,4-difluorocyclohexanecarboxylic acid from ethyl 4,4-difluorocyclohexanecarboxylate was as follows: ethyl 4,4-difluorocyclohexanecarboxylate (0.385 g, 2.003 mmol) was dissolved in THF (12 mL), and H2O (6 mL) was added, followed by lithium hydroxide monohydrate (0.420 g, 10.02 mmol). The reaction mixture was stirred vigorously at room temperature overnight. Upon completion of the reaction, the mixture was diluted with EtOAc and the pH was adjusted to 4 with 1 M HCl. The organic and aqueous layers were separated, and the aqueous layer was then extracted with EtOAc (1 time). The organic phases were combined, washed with brine, dried over MgSO4 and concentrated to dryness to give 4,4-difluorocyclohexanecarboxylic acid (318 mg, 97% yield) as a white solid.1H NMR (400 MHz, DMSO-d6): δ 12.28 (s, 1H), 2.40 (m, 1H), 2.02-1.75 (m, 6H), 1.59 (m, 2H) .
References
[1] Patent: US2014/275080, 2014, A1. Location in patent: Paragraph 0428
[2] Patent: WO2013/13188, 2013, A1. Location in patent: Paragraph 00313; 00314
[3] Patent: US9416132, 2016, B2. Location in patent: Page/Page column 134; 135
[4] Organic Letters, 2018, vol. 20, # 16, p. 4959 - 4963
[5] Patent: US2008/146605, 2008, A1. Location in patent: Page/Page column 39-40
