Benzyl Bromide → (4aS,7S,8R,9S,9aS)-8,9-bis(benzyloxy)-7-(4-chloro-3-(4-ethoxybenzyl)phenyl)-2-phenylhexahydro-4a,7-epoxy[1,3]dioxino[5,4-c]oxepine

Participants

Reaction Conditions

Reaction Steps

To a mixture of sodium hydride (6.5 g, 163.8 mmol, 60% dispersion in Mineral oil) in anhydrous tetrahydrofuran (30 mL) was added dropwise a solution of (4aS,7S,8R,9R,9aS)-7-(4-chloro-3-(4-ethoxybenzyl)phenyl)-2-phenylhexahydro-4a,7-epoxy[1,3]dioxino[5,4-c]oxepine-8,9-diol 28b (14.3 g, 27.3 mmol) in anhydrous tetrahydrofuran (10 mL) at 0° C. The mixture was stirred at 0° C. for 30 min and room temperature for 1 hour. To the mixture were added benzyl bromide (13 g, 109.2 mmol) and a catalytic amount of tetrabutylammonium iodide at 0° C. The resulting mixture was stirred at room temperature for 12 hours. The reaction mixture was quenched with water at 0° C., adjusted with saturated aqueous ammonium chloride till pH becomes 7 and extracted with ethyl acetate (100 mL×3). The combined organic layers were washed with saturated aqueous sodium chloride (30 mL×2), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel chromatography eluted with PE/EtOAc(v/v)=10/1 to give the title compound 28c as a white solid (17.6 g, 91.4%). The compound was characterized by the following spectroscopic data: 1H NMR (400 MHz, CDCl3) δ (ppm): 7.44-7.41 (m, 4H), 7.37 (m, 4H), 7.35-7.30 (m, 5H), 7.21 (d, 1H), 7.16 (m, 2H), 7.08 (d, 2H), 6.86 (d, 2H), 6.78 (d, 2H), 5.67 (s, 1H), 4.94 (d, 1H), 4.79 (d, 1H), 4.73 (s, 1H), 4.64 (d, 1H), 4.39 (d, 1H), 4.25 (d, 1H), 4.18 (d, 1H), 4.07-3.94 (m, 6H), 3.87 (d, 1H), 3.72 (d, 1H), 1.41 (t, 3H).

Provenance & Evidence