Process for 1-oxacephem derivatives

Abstract

A process for preparing compounds of the formula ##STR1## in which R is hydrogen or methoxy, R.sub.1 is a hydroxyl group, R.sub.2 is chlorine, bromine, OAc or SHET, R.sub.3 is hydrogen or a cleavable carboxy-protecting group preferably selected from loweralkyl, benzyl, benzhydryl, loweralkoxyloweralkyl, loweralkoxybenzyl, phenacyl, trimethylsilyl, 2,2,2-trichloroethyl or pivaloloxy, R.sub.4 is hydrogen or a cleavable amino-protecting acyl group, or R.sub.4 NH represents phthalimido, and HET is a five or six membered aromatic heterocycle containing 1-4 heteroatoms and optionally substituted with loweralkyl, and from which the corresponding 1-oxacephem derivatives can be prepared is described. The novel intermediate compounds of the formula 1 are produced from a penicillin derivative of formula 1 wherein R, R.sub.3 and R.sub.4 are as above described and R.sub.1 and R.sub.2 are both the same halogen, by treatment with a formylating agent in a halogenated hydrocarbon solvent to obtain the corresponding compound in which R.sub.1 and R.sub.2 are both OCHO which is then treated with less than one molar equivalent of a boron halide to obtain a 2:1 to 4:1 mixture of the corresponding compounds of formula 1 in which R.sub.1 is OCHO and R.sub.2 is the corresponding halogen or R.sub.1 is halogen and R.sub.2 is OCHO, and in which the former compound predominates. This mixture is separated and the compound in which R.sub.1 is OCHO and R.sub.2 is halogen is isolated. This last compound is hydrolyzed and the desired intermediate compound in which R.sub.1 is OH and R.sub.2 is a halogen is isolated. Alternatively, the compound of formula 1 in which R.sub.1 is OCHO and R.sub.2 is halogen is subjected to displacement by .sup.- OAc or HSHET prior to the hydrolysis.

Dependencies are inferred from the claim text.