Methanol → t-Butyl (6R,7R)-7-Amino-3-(tetrahydrofuran-2-yl)ceph-3-em-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

Phosphorus pentachloride (1.538 g, 7.5 mmol) in dichloromethane (39 ml) was added to t-butyl(6R,7R)-7-phenoxyacetamido-3-[(RS)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylate (2.267 g, 4.9 mmol) and N-methylmorpholine (1.1 ml, 10 mmol) in dichloromethane (20 ml) at -25° C. The reaction was stirred at -10±5° C. for 0.75 h then methanol (10 ml) added all at once, stirred 0.75 h then water (20 ml) added and stirred vigorously for 1 h. The dichloromethane was evaporated in vacuo, the aqueous residue washed with ether then adjusted to pH7 with ammonium hydroxide in the presence of ethyl acetate. The mixture was extracted twice with ethyl acetate, the extracts dried, concentrated and flash chromatographed on silica gel eluting with 30,40,50% ethyl acetate in hexane to give the more mobile (S)-diastereoisomer of the title compound (0.431 g, 27%); (Found: M+, 326.1299. C15H22N2O4S requires M, 326.1300); νmax (CH2Cl2) 1777, 1716, 1158 and 1052 cm-1 ; δH (CDCl3, 250 MHz) 1.52 (9H,s), 1.55-1.8 (1H, m), 1.85-2.05 (4H, m), 2.3-2.45 (1H, m), 3.30 and 3.59 (2H, ABq, J18.4 Hz), 3.8-4.0(2H,m), 4.75 (1H, d, J5.0 Hz) and 4.9-5.0 (2H, m). Further elution with 60% ethyl acetate in hexane gave the more polar (R)-diastereoisomer (0.533 g, 33%); (Found: M+ 326.1299. C15H22N2O4S requires M, 326.1300) νmax (CH2Cl2) 1776, 1721, 1158 and 1052 cm-1 ; δH (CDCl3, 250 MHz) 1.41 (2H, bs), 1.54 (9H, s), 1.6-1.85 (1H, m), 1.9-2.05 (2H, m), 2.05-2.2 (1H, m), 3.40 and 3.55 (2H, ABq, J17.8 Hz) 3.8-4.0 (2H, m), 4.67 (1H, d, J5.0 Hz), 4.93 (1H, d, J5.0 Hz), 5.0-5.15 (1H, m).

Provenance & Evidence