Hydrochloric Acid → 2,2-Difluoro-4-pentenoic acid

Participants

Reaction Steps

To a solution of ethyl α,α-difluoropentenoate 8b (80 g, 0.49 mol, U.S. Pat. No. 4,847,401, issued Jul. 11, 1989) in H2O (80 mL) is added LiOH (20.9 g, 0.5 mol) over 5 min at 0°-5° C. The reaction mixture is allowed to warm to room temperature for 3 h, then heated at 45°-50° C. for 3 h. Ethanol and H2O are removed (60 torr, 45° C.) from the reaction mixture. The resulting orange oil is dried (1 torr, room temperature) for 2 h to obtain an oily solid. The oily solid is diluted in H2O (75 mL) and acidified to pH 1 using conc HCl. The reaction mixture is extracted with diethyl ether (3×150 mL). Conc HCl is added to the aqueous layer until it is pH 1 and the aqueous layer is extracted again with diethyl ether (3×100 mL). The combined organic layers are dried (MgSO4), concentrated to an oil and distilled (140°-170° C.) to obtain 58.8 g, 432 mmol of the title compound 8c as an oil in 88% yield. 19F NMR (CDCl3) δ -106.8 (t)(CFCl3 as ref); 13C NMR (CDCl3) δ 168.3 (t, CO2H), 126.4 (s, C=C), 122.3 (s, C=C), 115.0 (t, CF2), 38.9 (t, CH2); 1H NMR (CDCl3) δ 2.88 (m, CH2, 2H), 5.28 (m, 1H), 5.32 (s, 1H), 5.76 (m, 1H), 8.74 (s, 1H).

Provenance & Evidence