HCID 88819542, compound → HCID 70636605, compound

Participants

Reaction Steps

As in the case of the aforedescribed reaction of amines with the 3-isocyanato-2-cephems, the reaction of such isocyanates with carbanionic reagents is accompanied by the rearrangement of the double bond in the cephem ring. Thus, benzhydryl 7-benzyloxycarbonylamino-3-isocyanato-2-cephem-4-carboxylate reacts with 1.1 equivalents of sodium diethylmalonate in tetrahydrofuran at -20° C. over a 5 minute period, to provide after hydrolysis with about 3 equivalents of 1N.HCl, benzhydryl 7 -benzyloxycarbonylamino-3-di(ethoxycarbonyl)acetamido-3-cephem-4-carboxylate. Likewise tert-butyl 7-(3-chlorophenylacetamido)-3-isocyanato-2-cephem-4carboxylate reacts with about 1.1 equivalents of isopropylmagnesium bromide in tetrahydrofuran at about --70° C. over a 30 minute period to give, upon acid hydrolysis, tert-butyl 7-(2-chlorophenylacetamido)-3-(2-methyl-propionamido)-3-cephem-4-carboxylate. The reaction of methyllithium with 4-methoxybenzyl 7-acetamido-3-isocyanato-3-cephem-4-carboxylate under similar conditions yields 4-methoxybenzyl 7-acetamido-3-acetamido-3-cephem-4-carboxylate.

Provenance & Evidence