78% |
With triethylamine; In dichloromethane; at 0 - 20℃;Inert atmosphere; |
Methanesulfonyl chloride (0.18 mL, 2.29 mmol) was added slowly dropwise to a stirred solution of 8-tert-butoxycarbonylamino-3,6-dioxaoctan-1-ol (0.52 g, 2.08 mmol) and TEA (0.44 mL, 3.12 mmol) in anhydrous CH2Cl2 (10 mL) at 0 C under N2 atmosphere. The reaction mixture was allowed to slowly warm to rt before being left to stir overnight. After this time, the reaction was quenched by the addition of ice cool water (10 mL) and the two phases were separated. The organic layer was washed with a saturated aqueous solution of NaHCO3 (10 mL) followed by brine (10 mL) and dried (MgSO4). The solvent was removed under reduced pressure and the crude residue obtained was purified by column chromatography (EtOAc/petroleum ether (40-60 C), 4:6) to give the intermediate, 8-tert-butoxycarbonylamino-3,6-dioxaoct-1-yl methanesulfonate (0.53 g, 78%), as a colourless oil: Rf 0.46 (EtOAc/MeOH, 95:5); numax (film) 2976, 2935, 2874, 1708, 1521, 1352, 1175 cm-1; deltaH (200 MHz; CDCl3) 1.38 (9H, s, C(CH3)3), 3.01 (3H, s, OSO2CH3), 3.24 (2H, br dt, NHCH2CH2O), 3.47 (2H, t, J 5.3, NHCH2CH2O), 3.58-3.61 (4H, m, OCH2CH2O), 3.71 (2H, t, J 4.6, OCH2CH2OSO2), 4.33 (2H, t, J 4.6, OCH2CH2OSO2), 4.93 (1H, br s, NH); deltaC (50 MHz; CDCl3) 28.6, 37.9, 40.5, 69.2, 69.4, 70.4, 70.5, 70.8, 79.5, 155.8; m/z (CI) 345 ([M+NH3]+, 17%), 328 ([M+H]+, 20), 289 (70), 271 (100), 228 (35); HRMS (ESI) m/z: [M+H]+, found 328.1426. C12H26NO7S requires 328.1424. |