Cyclopentanecarboxylic acid, 3,3-difluoro-, ethyl ester synthesis

Yield:1042153-25-2 61%

Reaction Conditions:

with diethylamino-sulfur trifluoride in dichloromethane; for 72 h;Reflux;Reagent/catalyst;

Steps:

4 4.4 Ethyl 3,3-difluorocyclopentane carboxylate (25)

To a solution of DAST (45.1g, 37.0mL, 282mmol) in CH₂Cl₂ (450mL) a solution of 22 (11.0g, 70.4mmol) in CH₂Cl₂ (150mL) was added at rt. The reaction mixture was refluxed until the starting material had disappeared (ca. 72h, monitored by ¹H NMR probe), then cooled, and saturated aq NaHCO₃ was added to pH=7. The aqueous phase was extracted with CH₂Cl₂ (2×100mL), the combined organic extracts were dried over Na₂SO₄ and evaporated in vacuo. The residue was distilled under reduced pressure. Yield 7.71g, 61%. Colorless oil. Bp 31-32°C/1.8mbar. ¹H NMR (CDCl₃, 400MHz): δ=4.17 (q, J=7.1Hz, 2H), 3.05-2.93 (m, 1H), 2.47-2.31 (m, 2H), 2.28-1.97 (m, 4H), 1.27 (t, J=7.1Hz, 3H). ¹³C NMR (CDCl3, 101MHz): δ=173.3, 131.2 (dd, J=250, 246Hz), 60.6, 40.6 (dd, J=5.4, 2.9Hz), 38.1 (t, J=26.6Hz), 34.7 (t, J=25.2Hz), 26.2 (dd, J=4.4, 3.5Hz), 13.9. ¹⁹F NMR (CDCl₃, 376MHz): δ=-92.0 (dquint, J=229, 16.4Hz), -93.2 (dquint, J=229, 16.4Hz). MS (EI): m/z=178 (M⁺), 158 (M⁺-HF). Anal. Calcd for C₈H₁₂F₂O₂: C, 53.93; H, 6.79. Found: C, 53.89; H, 6.39.

References:

Melnykov, Kostiantyn P.;Nosik, Pavel S.;Kurpil, Bohdan B.;Sibgatulin, Dmitriy A.;Volochnyuk, Dmitriy M.;Ryabukhin, Sergey V.;Grygorenko, Oleksandr O. [Journal of Fluorine Chemistry,2017,vol. 199,p. 60 - 66]