反应详情

t-Butyl (6R, 7R)-7-phenoxyacetamido-3-(tetrahydrothien-2-yl)ceph-3-em-4-carboxylate (0.375 g), high Rf diastereoisomer in dry dichloromethane (5 ml) was cooled to -20° C. under argon and treated with N-methylmorpholine (0.175 g, 0.19 ml). A solution of phosphorous pentachloride (0.214 g) in dichloromethane (5.3 ml) was added. After 30 min. a sample showed no starting material (by i.r.). Methanol (3 ml) was added rapidly in one portion and then allowed to warm to room temperature. After 1 h water (5 ml) was added and the solution vigorously stirred for 30 min. The solvent was removed in vacuo and ethyl acetate added. The pH was adjusted to 7 with concentrated aqueous ammonia solution. Flash chromatography on silica gel with 50 and 60% ethyl acetate/hexane gave the more mobile diastereoisomer of the title compound as a pale yellow foam (0.104 g, 39%); (Found: M+, 342.1081. C15H22N2O3S2 requires M, 342.1072); νmax (CH2Cl2) 1776 and 1716 cm-1 ; δH (CDCl3) 1.56 (10H, s overlapping m), 1.79-1.99 (3H, m collapses to 1H, m on D20), 2.22-2.33 (1H, m), 2.42-2.53 (1H, m), 2.98 (2H, dd, J 4.0, 8.9 Hz), 3.36 and 3.74 (2H, ABq, J 17.9 Hz), 4.73 and 4.93 (2H, ABq, J 5.0 Hz) and 4.88 (1H, dd, J 6.5, 9.9 Hz). The second, more polar diastereoisomer of the title compound, was obtained as a pale yellow solid (0.079 g, 29%); (Found: M+, 342.1085. C15H22N2O3S2 requires M, 342.1072); νmax (CH2Cl2) 1777 and 1718 cm-1 ; δH (CDCl3) 1.57 (9H, s), 1.66-2.99 (4H, m collapses to 2H, m on D20), 2.03-2.14 (1H, m), 2.23-2.35 (1H, m), 2.96 (2H, dd, J 4.2, 8.6 Hz), 3.43 and 3.75 (2H, ABq, J 17.1 Hz), 4.69 and 4.96 (2H, ABq, J 5.0 Hz) and 4.79 (1H, dd, J 6.1, 9.9 Hz).

1. customThe solvent was removed in vacuo and ethyl acetate
2. additionadded