Sodium hydride → [(R)-2-(2,2-diethoxyethoxy)-4-pentenyloxymethyl]benzene

Participants

Reaction Conditions

Reaction Steps

A solution of (2R)-1-(benzyloxy)pent-4-en-2-ol (C1) (material from the previous step, ≦60 mmol) in tetrahydrofuran (50 mL) was added drop-wise to a suspension of sodium hydride (60% in mineral oil, 11.0 g, 275 mmol) in tetrahydrofuran (100 mL) at 0° C. After the reaction mixture had stirred for 30 minutes at this temperature, a solution of 2-bromo-1,1-diethoxyethane (97%, 13.3 mL, 85.8 mmol) in tetrahydrofuran (50 mL) was added at 0° C., and the reaction mixture was heated at reflux for 18 hours. Additional 2-bromo-1,1-diethoxyethane (11 mL, 71 mmol) was added, and heating was continued for a further 24 hours. The reaction mixture was cooled to 0° C., quenched with water, and extracted three times with ethyl acetate. The combined organic layers were washed with water, washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. Chromatography on silica gel (Gradient: 0% to 15% ethyl acetate in heptane) afforded the product as a colorless oil. Yield: 11.04 g, 35.80 mmol, 60% over 2 steps. 1H NMR (400 MHz, CDCl3) δ 1.21 (t, J=7.1 Hz, 3H), 1.22 (t, J=7.0 Hz, 3H), 2.31-2.36 (m, 2H), 3.49-3.74 (m, 9H), 4.55 (s, 2H), 4.61 (t, J=5.3 Hz, 1H), 5.02-5.12 (m, 2H), 5.78-5.90 (m, 1H), 7.27-7.38 (m, 5H).

Provenance & Evidence