反应详情

To a solution of Paclitaxel (52.5 mg; 0.061 mmol) and imidazole (40.1 mg; 0.590 mmol) in 0.25 mL of dry DMF under nitrogen was added the crude benzyl 5-(chlorodimethylsilyl)pentanoate of undetermined titre. A total of 197 mg of crude silyl chloride was added in 4 portions along with an additional 12 mg portion of imidazole over a 29 hour period. After stirring for an additional 12 hours, the reaction mixture was concentrated under reduced pressure and the resulting crude material was purified by column chromatography (silica gel, 0-50% ethyl acetate in hexanes, 40 minute gradient) to give 33 mg (27%) of (2aR,4S,4aS,6R,9S,11S,12S,12bS)-9-(((2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl)oxy)-12-(benzoyloxy)-4-(((5-(benzyloxy)-5-oxopentyl)dimethylsilyl)oxy)-11-hydroxy-4a,8,13,13-tetramethyl-5-oxo-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxete-6,12b-diyl diacetate as a white waxy solid. 1H NMR (500 MHz, CDCl3) δ 8.14-8.10 (m, 2H), 7.77-7.74 (m, 2H), 7.61 (dddd, J=1.3, 1.3, 7.4, 7.4 Hz, 1H), 7.52-7.46 (m, 5H), 7.43-7.38 (m, 4H), 7.36-7.29 (m, 6H), 7.07 (d, J=8.9 Hz, 1H), 6.38 (s, 1H), 6.17 (dd, J=9.6, 8.4 Hz, 1H), 5.80 (dd, J=9.0, 2.4 Hz, 1H), 5.67 (d, J=7.0 Hz, 1H), 5.11 (s, 2H), 4.90 (d, J=9.4 Hz, 1H), 4.79 (s, 1H), 4.37 (dd, J=10.3, 6.9 Hz, 1H), 4.29 (d, J=8.4 Hz, 1H), 4.18 (d, J=8.4 Hz, 1H), 3.80 (d, J=6.9 Hz, 1H) 3.63 (s, 1H), 2.45 (ddd, J=14.4, 9.5, 6.8 Hz, 1H), 2.37 (s, 3H), 2.37-2.33 (m, 2H), 2.31 (dd, J=8.8, 5.4 Hz, 1H), 2.16 (s, 3H), 1.88-1.81 (m, 3H), 1.68 (s, 3H), 1.66-1.61 (m, 3H), 1.34-1.27 (m, 2H), 1.21 (s, 3H), 1.18 (s, 3H), 0.92-0.82 (m, 2H), 0.60-0.48 (m, 2H), 0.08 (s, 3H), 0.07 (s, 3H). MS (ESI+) m/z 1102.4 (M+1); HPLC 96% (AUC), tR 22.72 min (Method A).

1. concentrationthe reaction mixture was concentrated under reduced pressure
2. customthe resulting crude material was purified by column chromatography (silica gel, 0-50% ethyl acetate in hexanes, 40 minute gradient)