PROCESS FOR PREPARING DESACETOXYCEPHALOSPORINS FROM PENICILLIN SULFOXIDES AND NEW SILYLESTERS OF AZETIDINE - 2 - SULFENATES

摘要

1412856 Silyl 3-amido-4-oxo-azetidine-2- sulphenates ELI LILLY & CO 30 April 1973 [10 May 1972 12 April 1973] 20348/73 Heading C3S [Also in Division C2] Silyl esters of azetidine-2-sulphenates of Formula II in which each R 1 is independently C 1 -C 4 alkyl or phenyl; R 2 is C 1 -C 6 alkyl, 2,2,2-trihaloethyl, 2-iodoethyl, benzyl, nitrobenzyl, tetrahydropyranyl, 9-fluoranyl, succinimidomethyl, phthalimidomethyl; methoxybenzyl, dimethoxybenzyl, cyanomethyl, nitrophenyl, dinitrophenyl, 2,4,6 - trinitrophenyl, bis- (2 - methoxyphenyl) methyl, triphenylmethyl, benzhydryl, benzyloxymethyl, C 2 -C 6 alkanoyloxymethyl C 2 -C 4 alkanoyl, phenacyl, or a radical of formula in which each R 1 is as defined above, R 3 is H and R 4 is C 1 -C 8 alkanoyl; azidoacetyl; cyanoacetyl; haloacetyl; in which Ar is phenyl, thienyl, furyl, pyrrolyl, or phenyl substituted with one to three of chlorine, fluorine, bromine or iodine, trifluoromethyl, C 1 -C 3 acyloxy, -OSi(R 1 ) 3 , where R 1 is as defined above, C 1 -C 3 alkyl, C 1 -C 3 alkoxy cyano and nitro; where ArSP1/SP is phenyl, pyridyl, or substituted phenyl as above and Y is O or S; in which Ar is as above, B is C 1 -C 3 acyloxy, where R 1 is as above, esterified carboxyl, -CN, -N 3 , or -NHR, where R is benzyloxycarbonyl, cycloalkoxycarbonyl, triphenylmethyl, 2,2,2 - trichloroethoxycarbonyl or -Si(R 1 ) 3 in which R 1 is as above; (3-sydnone) C 2 -C 3 alkanoyl; in which RSP1/SP is H or -OCH 3 ; 2-(1H-tetrazol-1 yl) acetyl; or R 3 and R 4 taken together with the N atom to which they are attached 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 are prepared by heating a penicillin sulphoxide of formula wherein R 2 , R 3 and R 3 are as defined above, or R 2 and R 4 may be hydrogen, in an inert, substantially anhydrous solvent to a temperature of from about 75‹ C. to about 150‹ C. in the presence of a silylating agent containing at least one cleavable moiety of formula in which each R 1 is independently C 1 -C 4 alkyl or phenyl. The silyl esters may be converted to the corresponding desacetoxycephalosporin by treatment with an acidic compound in an inert, anhydrous solvent. (See Division C2).