2,2,2-Trifluoroethanol → 2,2,2-Trifluoroethyl 3-(2-(2-allyloxy-ethoxy)-ethoxy)-propanoate

Participants

Reaction Steps

To a stirred solution of alcohol (9) (8.77 g, 60.0 mmol, 2.2 equiv.) in THF (100 mL) was added freshly hexanes-degreased Na (0.2 g, 8.7 mmol, 0.3 equiv.) in small portions at room temperature. The reaction was then stirred at room temperature for 1 h (until the Na chunks disappeared). A solution of ethyl acrylate (2.97 mL, 27.3 mmol, 1.0 equiv.) in THF (30 mL) was then added dropwise (30 min) through an addition funnel. After 2 h at room temperature, the reaction was quenched with 10 drops of glacial acetic acid then submitted to a CHCl3/H2O extraction. The combined organic layers were dried over anhydrous MgSO4, filtered then evaporated under reduced pressure to provide crude ester (10). The latter was diluted with a 1/1 (v/v) mixture of MeOH (120 mL) and 2.5 M KOH aqueous solution (120 mL). The reaction was vigorously stirred at room temperature overnight then extracted with CHCl3. The aqueous layer was carefully acidified with concentrated (38%) HCl then extracted with CHCl3. The combined organic layers were dried over anhydrous MgSO4, filtered then evaporated under reduced pressure to provide crude acid (11). The latter (4.05 g, 18.6 mmol, 1.0 equiv.) was diluted with CH2Cl2 (120 mL) then DCC (4.25 g, 20.4 mmol, 1.1 equiv.), 2,2,2-trifluoroethanol (1.50 mL, 20.4 mmol, 1.1 equiv.) and 4-DMAP (0.23 g, 1.9 mmol, 0.1 equiv.) were successively added. The reaction was stirred at room temperature overnight then filtered through a short plug of Celite (CH2Cl2 washings). After evaporation of the filtrate under reduced pressure, the final purification was achieved by column chromatography on silica gel (Hexanes/EtOAc gradient) and provided 3.59 g (44%, 3 steps) of ester (12) as a pale yellow oil; 1H NMR (400 MHz, CDCl3) δ 5.92 (m, 1H), 5.28 (m, 1H), 5.18 (m, 1H), 4.49 (q, J=8.4 Hz, 2H), 4.03 (m, 2H), 3.79 (t, J=6.4 Hz, 2H), 3.63 (m, 8H), 2.71 (t, J=6.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 170.2, 134.9, 123.1 (q, J=275.7 Hz), 117.2, 72.4, 70.9, 70.8, 70.7, 69.6, 66.3, 60.5 (q, J=36.5 Hz), 34.8; IR (neat) 1760 cm−1; HRMS (ESI, m/z) calcd. for C12H20O5F3 (MH+) 301.1257, found 301.1258.

Provenance & Evidence