Process for preparing desacetoxycephalosporins

Claim 1

A process for preparing a desacetoxycephalosporin from a penicillin sulfoxide of the formula ##SPC7## in which R 3 is hydrogen and R 4 is hydrogen; C 1 -C 8 alkanoyl; azidoacetyl; cyanoacetyl; haloacetyl; ##EQU16## in which Ar is phenyl, thienyl, furyl, pyrrolyl, or phenyl substituted with from one to three substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, trifluoromethyl, C 1 -C 3 acyloxy, hydroxy, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, cyano, and nitro; ##EQU17## in which Ar' is phenyl, pyridyl, or substituted phenyl as defined above, and Y is oxygen or sulfur; ##EQU18## in which Ar is as defined above, and B is C 1 -C 3 acyloxy, hydroxyl, carboxyl, esterified carboxyl, --CN, --N 3 , --NH 2 , or --NHR in which R is benzyloxycarbonyl, C 1 -C 4 alkoxycarbonyl, cycloalkoxycarbonyl, triphenylmethyl, ##EQU19## or 2,2,2-trichloroethoxycarbonyl; (3-sydnone)-C 2 -C 3 alkanoyl; ##SPC8## in which R' is hydrogen or methoxy; 2-(1H-tetrazol-1-yl)acetyl; or R 3 and R 4 taken together with the nitrogen atom to which they are bonded are phthalimido, a cyclic imide moiety of a C 3 -C 12 dicarboxylic acid, 2,2-dimethyl-5-oxo-4-phenylimidazolidin-1-yl, or 2,2-dimethyl-3-nitroso-5-oxo-4-phenylimidazolidin-1-yl; and R 2 is hydrogen, C 1 -C 6 alkyl, 2,2,2-trihaloethyl, 2-iodoethyl, benzyl, nitrobenzyl, tetrahydropyranyl, 9-fluorenyl, succinimidomethyl, phthalimidomethyl, methoxybenzyl, dimethoxybenzyl, cyanomethyl, nitrophenyl, dinitrophenyl, 2,4,6-trinitrophenyl, bis(p-methoxyphenyl)methyl, triphenylmethyl, benzhydryl, benzyloxymethyl, C 2 -C 6 alkanoyloxymethyl, C 2 -C 4 alkanoyl, phenacyl, or a radical of the formula ##EQU20## in which each R 1 independently is c 1 -C 4 alkyl or phenyl; which comprises heating the penicillin sulfoxide in an inert, substantially anhydrous solvent to a temperature of from about 75°C. to about 150°C. in the presence of from about 1.1 to about 4 equivalents of a silylating agent of the formula a. ##EQU21## in which each R 1 independently is C 1 -C 4 alkyl, or phenyl, R'" is hydrogen, C 1 -C 4 alkyl, or phenyl, and X is ##EQU22## in which J is hydrogen or --Si(R 1 ) 3 , or X is --CW 3 in which each W independently is hydrogen, trifluoromethyl or C 1 -C 3 alkyl; b. ##EQU23## in which R 1 and W are as herein defined; and c. Z--Si(R 1 ) 3 in which R 1 is as herein defined and Z is halogen, C 2 -C 3 alkenyloxy, C 1 -C 3 alkyl--SO 3 --, --O--Si(R 1 ) 3 , --S--Si(R 1 ) 3 , or ##EQU24## in which R 5 is hydrogen or c 1 -C 3 alkyl, and R 6 is C 1 -C 4 alkyl or --Si(R 1 ) 3 , or R 5 and R 6 taken together with the nitrogen atom to which they are bonded form a heterocyclic ring having 5 or 6 atoms, up to 3 of which, in addition to the already-defined nitrogen atom, independently are nitrogen, sulfur, or oxygen; and simultaneously or subsequently treating the reaction mixture in an acidic medium selected from the group consisting of a mineral acid, a sulfonic acid, and a Lewis acid.