Dichloromethane → 3-Cephem

Participants

Reaction Steps

A solution of 731 mg (1 mmol) of a 1:1 mixture consisting of 2-[4-(p-toluenesulphonylthio)-3-phenoxyacetamido-2-oxoazetidin-1-yl]-3-benzoxy-crotonic acid p-nitrobenzyl ester and the corresponding isocrotonic acid p-nitrobenzyl ester in a mixture of 0.185 ml (1.2 mmols) of 1,5-diazabicyclo[5.4.0] undec-5-ene in 20 ml of dry tetrahydrofurane is stirred for precisely 35 minutes at room temperature. 50 ml of methylene chloride are added to the mixture and the whole is washed successively with dilute hydrochloric acid, water and dilute aqueous sodium bicarbonate solution. The organic phase is dried over sodium sulphate and concentrated by evaporation in vacuo. The residue is chromatographed on 25 mg of acid-washed silica gel, using toluene/ethyl acetate (3:1). A mixture consisting of the ceph-2-em compound and the ceph-3-em compound in the ratio of about 3:1 is obtained; this mixture can be separated by repeated chromatography into the pure isomers, giving 7β-phenoxyacetamido-3-benzoxy-ceph-2-em-4α-carboxylic acid p-nitrobenzyl ester of melting point 160° C.-162° C. (diethyl ether/pentane); IR spectrum (methylene chloride): characteristic bands at 5.6, 5.7, 5.9 and 7.4 μ, and 7β-phenoxyacetamido-3-benzoxy-ceph-3-em-4-carboxylic acid p-nitrobenzyl ester in the form of a colourless foam, IR spectrum (methylene chloride): characteristic bands at 5.6, 5.8 sh, 5.9, 7.9 and 8.4 μ.

Provenance & Evidence