Methanesulfonyl chloride → Benzyl alpha-[3-benzyl-7-oxo4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl]-alpha-(1-methanesulfonyloxyethylidene)acetate

Participants

Reaction Steps

One adds to a solution of benzyl α-[3-benzyl-7-oxo-4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl]-α-(1-hydroxyethylidene)acetate (1.424 g) in tetrahydrofuran (15 ml), triethylamine (0.96 ml), and methanesulfonyl chloride (0.28 ml) at -30° to -20° C, stirs for 55 minutes to give benzyl α-[3-benzyl-7-oxo-4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl]-α-(1-methanesulfonyloxyethylidene)acetate, adds morpholine (0.40 ml) and stirs for 5 hours at -10° C to -3° C to give benzyl α-[3-benzyl-7-oxo-4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl]-α-(1-morpholinoethylidene)-acetate, cools to -35° C to -30° C, adds pyridine (0.27 ml) and bromine in carbon tetrachloride (1 mmole/ml: 3.2 ml), and stirs for 20 minutes to give benzyl α-[3-benzyl- 7-oxo-4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl]hept-2-en-6-yl]-α-(1-morpholino-2-bromoethylidene)acetate, adds 5% hydrochloric acid (13 ml) and methanol (50 ml), and kept at 0° C overnight to hydrolyze and cyclize giving the cephem product. The solvent is removed under reduced pressure, and the residual solution is extracted with ethyl acetate. The extract solution is washed with saturated saline and water, dried over sodium sulfate, and purified by chromatography over silica gel containing 10% water. The fractions containing the product are combined and evaporated. Recrystallization of the residue from a mixture of methanol, ether, and hexane gives benzyl 7-phenylacetamido-3-hydroxy-3-cephem-4-carboxylate. m.p. 149°-162° C. NMR: δCDCl3 3.28d2H, 3.63s2H, 4.98d(5Hz)1H, 5.30s2H, 5.60dd (5;8Hz)1H, 6.37d(8Hz)1H, 7.4s+7.4s1OH, 11.6brs1H. IR: νmaxCHCl3 3420, 1785, 1680, 1615 cm-1.

Provenance & Evidence