Reaction Steps
A solution of (2S,3R,4S)-2-((4-methoxybenzyl)oxy)-7-methyl-4-vinyloctan-3-ol (2.0 g, 6.53 mmol) in anhydrous DMF (12 mL) was added at room temperature to a solution of NaH (NaH; 0.326 g, 8.16 mmol, 60% dispersion in mineral oil) in anhydrous DMF (12 ml). The reaction was stirred for 15 minutes (min) at room temperature, treated with (bromomethyl)cyclopropane (0.823 ml, 8.48 mmol) at room temperature, and then was heated to 40° C. for and stirred for 6 h. The reaction was cooled to room temperature and additional NaH (0.131 g, 3.27 mmol) and (bromomethyl)cyclopropane (0.317 mL, 3.27 mmol) were added, and the reaction was heated at 45° C. for 4 h. The reaction was again cooled to room temperature and a third batch of NaH (0.131 g, 3.27 mmol) followed by (bromomethyl)cyclopropane (0.317 mL, 3.27 mmol) was added and the reaction was heated at 45° C. for 2 h. The reaction mixture was quenched with saturated aqueous ammonium chloride (NH4Cl) and the phases were separated. The aqueous phase was extracted with diethyl ether (Et2O), and the combined organic phases were washed with brine, dried over magnesium sulfate (MgSO4), concentrated, and purified by column chromatography on SiO2 (gradient, hexanes/ethyl acetate) to furnish the title product as a colorless oil (1.94 g, 82%): IR (neat) 2953, 2868, 1613, 1513, 1247, 1084 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.25-7.20 (m, 2H), 6.89-6.81 (m, 2H), 5.52 (dt, J=17.0, 10.0 Hz, 1H), 5.03-4.92 (m, 2H), 4.52-4.32 (m, 2H), 3.78 (s, 3H), 3.65-3.56 (m, 2H), 3.34 (dd, J=10.0, 6.9 Hz, 1H), 3.28-3.22 (m, 1H), 2.09 (tdd, J=10.1, 7.7, 3.1 Hz, 1H), 1.81-1.67 (m, 1H), 1.55-1.42 (m, 1H), 1.28-1.13 (m, 2H), 1.19 (d, J=6.3 Hz, 3H), 1.13-0.95 (m, 2H), 0.87 (d, J=6.4 Hz, 3H), 0.86 (d, J=6.8 Hz, 3H), 0.56-0.45 (m, 2H), 0.25-0.14 (m, 2H); ESIMS m/z 383.4 ([M+Na]+).
