Process for preparation of 2-chlorosusfinyl azetidinones

摘要

An improved method for preparing 2-chlorosulfinyl azetidine-4-one comprises heating a penicillin sulfoxide ester with an N-chlorohalogenating agent at a temperature of about 75 DEG C. to about 140 DEG in an inert organic solvent, and in the presence of an organic solvent insoluble, strongly basic ion exchange resin. Desirably, the ion exchange resin comprises a styrene-divinyl benzane copolymer which is about 2 to 16% cross-linked and incorporates a quaternary ammonium functionality. Such ion exchange resins are commercially available. The 2-chlorosulfinyl azetidine-4-one which is produced by this method can be cyclized in the presence of a Friedel-Crafts catalysts to afford the 3-exomethylene cepham sulfoxide ester in yields of 80-90%.