Synthetic routes to azetidinones related to nocardicin

A process for the manufacture of an azetidinone related to nocardicin having the formula (I):

• ##STR17## wherein R is a saturated or unsaturated alkyl having from 1 to 6 carbon atoms, .alpha.-aminobenzyl, benzyl, a free or substituted phenyl, the phenyl substituent being selected from hydroxy, methyl, methoxy, and amino;
• R.sub.1 is hydrogen, alkyl having from 1 to 4 carbon atoms, trimethylsilyl, trichloroethyl, benzhydryl, or benzyl;
• and
• R.sub.2 is a free or substituted phenyl, the phenyl substituent being selected from hydroxy, methyl, methoxy, and amino;
• comprising the steps of
• (a) reacting a compound of the formula (II):
• ##STR18## wherein R.sub.3 is phenyl or phenoxy, with a compound of formula YCHR.sub.2 COOR.sub.1, in which Y is a leaving group selected from the group consisting of iodine, bromine, chlorine, acyloxy, and sulphonyloxy, and in which R.sub.1 and R.sub.2 have the meanings set forth above;
• in the presence of a metal hydride in a solvent selected from the group consisting of anhydrous tetrahydrofuran, dimethylformamide, hexamethylphosphoramide, and their mixtures, at a temperature ranging from -30.degree. to 20.degree. C., to give a compound of the formula (III):
• ##STR19## (b) N-acylating the compound of formula (III), with concomitant shifting of the double bond to the extra-nuclear position, by reaction with an acyl halide RCOX, where X is halogen and R has the meaning stated above, in the presence of an organic base or a saturated aqueous solution of NaHCO.sub.3 in a two-phase system, thereby giving a compound of formula (IV):
• ##STR20## (c) hydrolytically cleaving the compound of formula (IV) by treatment with an aqueous solution of HCl in acetone, or by passing same through a silica gel column, thereby obtaining the 4-thioacyl derivative of formula (V):
• ##STR21## (d) and reductively desulphurizing the compound of formula (V) with Raney-Ni to yield the azetidinone (I).