Reaction Steps
Dry DMSO (19.36 mL, 273.6 mmol) in dry CH2Cl2 (35 mL) was added dropwise to a stirred solution of 2 M (COCl)2 (68.40 mL, 136.8 mmol) at −78° C. during 15 min. The alcohol 12 (24 g, 109.44 mmol), prepared according to Example 11 , in dry dichloromethane (50 mL) was then added during 10 min, resulting in a slightly cloudy solution. This was stirred for 30 min at −78° C. and a solution of triethyl amine (79 mL, 547.2 mmol) in dichloromethane (50 mL) was then added dropwise during 15 min. The mixture was stirred for 30 min at −78° C. and 30 min at 0° C. The reaction was quenched by adding water (25 mL) with rapid stirring. The resulting slurry was immediately poured into ether (300 mL) and washed with 20% KHSO4 (2×200 mL). The layers were separated and the aqueous layer was extracted with ether (2×100 mL). The combined organic layers were washed with brine solution (2×100 mL), dried over MgSO4, filtered, and concentrated to afford crude aldehyde 13 (22 g) which was immediately used for protection. A stirred solution of crude 13 (22 g, 101.25 mmol), ethylene glycol (9.4 g, 151.87 mmol), and p-toluenesulfonic acid monohydrate (1 g) in dry benzene (200 mL), contained in a 500 mL round-bottom flask fitted with a Dean Stark trap, was heated at reflux for 12 h. The mixture was cooled to room temperature, the benzene layer was separated, and the aqueous layer was extracted with ether (2×100 mL). The combined organic layers were dried over MgSO4 and filtered. The residue obtained on concentration was purified by column chromatography on silica gel, using ether/hexane (1:1) as eluant, to give acetal 14 (21 g, 73.5%) as an oil. IR (KBr) νmax 3066, 3030, 2927, 2881, 1642, 1457, 1400, 1365, 1208, 1156, 1100, 1028, 946, 739, 628 cm−1; 1HNMR (CDCl3) δ 1.62-1.66 (m, 1 H), 1.79-1.91 (m, 2 H), 2.08-2.11 (m, 1 H), 2.25-2.28 (m, 1 H), 3.54 (t, J=6.9 Hz, 2 H), 3.78-3.90 (m, 4 H), 4.47 (s, 2 H), 4.80 (d, J=3.8 Hz, 1 H), 4.97-5.04 (m, 2 H), 5.77-5.82 (m, 1 H), 7.23-7.34 (m, 5 H); 13CNMR (CDCl3) δ 28.55, 33.78, 38.33, 64.77, 64.86, 68.40, 72.59, 106.00, 116.04, 127.29, 127.45, 128.16, 136.66, 138.62; mass spectrum (EI), m/z (rel intensity) 262 (M+. 1.6), 171 (4.4), 156 (3.2), 149 (9), 128 (3.3), 114 (2.6), 109 (7), 105 (4.1), 99 (3.6), 92 (3.7), 91 (31), 81 (3.7), 77 (5), 73 (100), 67 (4), 65 (6).
