合成路线1

A new synthesis of loracarbef has been described: The reaction of L-(+)-phenylglycine (I) with ethyl chloroformate (II) and NaOH in dichloromethane gives L-N-(ethoxycarbonyl)phenylglycine (III), which is reduced with BH3 in THF to the alcohol (IV). The cyclization of (IV) by means of NaH in THF affords oxazolidinone (V), which by alkylation with ethyl bromoacetate and hydrolysis with NaOH is converted into the oxazolidinone-3-acetic acid (VI), and the corresponding acyl chloride (VII). The cyclization of (VII) with 2-[3-(benzylimino)-1-propenyl]furan (VIII) by means of triethylamine in dichloromethane yields the azetidinone (IX), which is purified from its enantiomer by crystallization. The reduction of (IX) with H2 over Pd/C in dichloromethane gives 1-benzyl-2-[2-(2-furyl)ethyl]-3-(2-oxo-4-phenyloxazolidin-3-yl)azetidin-4-one (X) with a 100% optical purity. The cleavage of (X) with Li/NH3 in tert-butanol - THF yields 3(S)-amino-2(R)-[2-(2-furyl)ethyl]azetidin-4-one (XI), which is acylated with phenoxyacetyl chloride (XII) and NaHCO3 to the amide (XIII). Ozonolysis of (XIII) with O3, H2O2 in dichloromethane-methanol affords 3-[4-oxo-3(S)-phenoxyacetamido)azetidin-2(R)-yl]propanoic acid (XIV), which is then condensed with the magnesium salt of the malonic derivative (XV) in THF to yield the ketoester (XVI).