Reaction Steps
A flame-dried round-bottom flask under argon atmosphere is charged with 458 mg (1.22 mmol, 1 equiv.) of starting material 20, 1.3 mL 1,2-dimethoxyethane, and 953 μL (5.34 mmol, 5.5 equiv.) diisopropylethylamine. With stirring, 376 μL (4.95 mmol, 5.1 equiv.) methoxymethyl chloride is added dropwise. The stirring reaction is heated to 60° C. for four hours before being allowed to cool to room temperature. Once the reaction has cooled, it is transferred to a separatory funnel in 50 mL hexane and the organic layer is washed sequentially with 10% aqueous hydrochloric acid, water, and brine. The organic solution is then dried with MgSO4 and concentrated in vacuo to give a clear to yellow oil. The crude product is purified by silica gel chromatography (Rf=0.25 in 4:1 hexane:ethyl acetate) to give 380 mg (97% yield) of 50 as a clear oil. 1H NMR (500 MHz, CDCl3) δ ppm 5.67 (s, 1H), 5.07 (tt, J=7.1, 1.4 Hz, 1H), 4.97 (tt, J=6.2, 1.3 Hz, 1H), 4.58 (dd, J=36.8, 7.0 Hz, 2H), 3.75 (s, 3H), 3.60 (dd, J=11.2, 5.5 Hz, 1H), 3.32 (s, 3H), 3.18 (s, 3H), 2.48 (dd, J=14.4, 6.2 Hz, 1H), 2.29-2.42 (m, 2H), 2.21 (dd, J=13.4, 5.4 Hz, 3H), 1.87 (ddt, J=18.3, 12.1, 5.5, 5.5 Hz, 3H), 1.78 (dd, J=13.3, 11.4 Hz, 3H), 1.65 (s, 12H), 1.57 (ddd, J=12.9, 4.6 Hz, 1H), 1.27 (ddd, J=12.9, 4.5 Hz, 1H), 0.92 (s, 3H). 13C NMR (126 MHz, CDCl3) δ ppm 205.2, 193.0, 177.3, 134.3, 131.8, 124.3, 119.1, 106.0, 97.1, 77.4, 76.9, 69.2, 57.1, 55.9, 55.8, 46.3, 37.6, 37.4, 29.6, 26.0, 25.9, 21.6, 18.1, 17.8, 16.5. HRMS-ESI (m/z): [M+H]+ calculated for C24H36O5, 405.2636. found 405.2637.
