Acylation of 7-aminocephalosporanic acid (I) with 2-thienyleacetyl chloride (II) in the presence of NaOH led to amide (III). The carboxylate group of (III) was then protected as the corresponding benzhydryl ester (IV) upon treatment with diphenyldiazomethane. Mitsunobu coupling of the hydroxymethyl cephem (IV) with triclosan (V), with partial double-bond isomerization, gave rise to a mixture of the desired delta-3 ether (VI) and its delta-2 isomer (VII), which were separated by repeated column chromatography. Isomerization was minimized by conducting the reaction at -20 C. Finally, removal of the benzhydryl ester group of (VI) was accomplished by treatment with trifluoroacetic acid in the presence of anisole.

Acylation of 7-aminocephalosporanic acid (I) with 2-thienyleacetyl chloride (II) in the presence of NaOH led to amide (III). The carboxylate group of (III) was then protected as the corresponding benzhydryl ester (IV) upon treatment with diphenyldiazomethane. Mitsunobu coupling of the hydroxymethyl cephem (IV) with triclosan (V), with partial double-bond isomerization, gave rise to a mixture of the desired delta-3 ether (VI) and its delta-2 isomer (VII), which were separated by repeated column chromatography. Isomerization was minimized by conducting the reaction at -20 C. Finally, removal of the benzhydryl ester group of (VI) was accomplished by treatment with trifluoroacetic acid in the presence of anisole.