Reaction Steps
To a stirred solution of 2 (117.0 g, 243.8 mmol) and Hunig's base (diisopropylethylamine, 63.0 g, 487.5 mmol) in CH2Cl2 (400 mL) at 23° C. was added a solution of benzyl chloromethyl ether (40.7 g, 260.0 mmol) over a 15 min. period. The resultant mixture was maintained at 23° C. and stirred for 14 h. Ether (1 L) was added to the mixture and the ethereal solution was washed with 10% aqueous HCl (1×100 mL) and H2O (200 mL). The organic layer was dried (MgSO4) and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (CH2Cl2/AcOEt 40:1 then 10:1) to yield 128.9 g (88%) of 3 as a white solid. Rf(CH2Cl2/AcOEt 10:1) 0.31. 1H-NMR (CDCl3): 1.10 (s, 9H, C-Me3), 1.65 (s, 3H, 5-Me), 2.16 (m, 1H, 2′-Hβ), 2.41 (m, 1H, 2′-Hβ), 2.53 (br s, 1H 3′-OH), 3.84 (d, 1H, J=8.8 Hz, 5′-CHH), 3.98 (d, 1H, J=8.8 Hz, 5′-CHH), 4.01 (s, 1H, 4′-H), 6.64 (br s, 1H, 3′-H), 4.70 (s, 2H, OCH2Ph), 5.50 (s, 2H, NCH2O), 6.41 (dd, 1H, J=8.0, 5.8 Hz, 1′-H), 7.20-7.50 (m, 13H, aromatic-H), 7.65-7.69 (m, 3H, 6-H and aromatic-H). 13C-NMR (CDCl3): 12.86 (−5-CH3), 19.45 (+, C-Me3), 27.09 (−, C-Me3), 41.16 (+, 2′-C), 64.25 (+, 5′-C), 70.70 (+, O—C—Ph), 71.97 (−, 4′-C), 72.29 (+, N—C—C), 85.51 (−, 3′-C), 87.20 (−, 1′-C), 110.47 (+, 5-C), 127.72, 128.08, 128.36 (−, aromatic-C), 130.25 (−, 6-C), 132.42, 133.00 (+, aromatic-C) 134.39, 135.37, 135.62 (−, aromatic-C), 137.95 (+, aromatic-C), 151.01 (+, 2-C), 163.68 (+, 4-C).
