PROCESS FOR OBTAINING 7-ACYLAMIDO-7-ALKOXY-CEPHALOSPORINS

1445743 Production of 7-amino and 7- acylamino-7-alkoxy cephalosporins ELI LILLY & CO 3 Oct 1973 [16 Oct 1972] 46093/73 Heading C2C Compounds of the formula wherein R‹ represents a primary C 1-4 alkyl group or -CD 3 ; R1 represents an acetoxy, carbamoyloxy, α - methoxy - p - hydroxycinnamoyloxy, propionyloxy, benzoyloxy, methoxy, methylthio, 1 - methyl - 1,2,3,4- tetrazol - 5 - ylthio, or 5 - methyl - 1,3,4- thiadiazol - 2 - ylthio radical; R2A represents hydrogen or R2; and R2 represents C 1-6 alkyl, 2,2,2 - trichloroethyl, 2 - iodoethyl, tert - C 5-7 - alkenyl, tert - C 5-7 - alkynyl, benzyl, nitrobenzyl, tetrahydropyranyl, succinimidomethyl, phthalimidomethyl, methoxybenzyl, dimethoxybenzyl, cyanomethyl, nitrophenyl, dinitrophenyl, 2,4,6 - trinitrophenyl, bis-(pmethoxyphenyl)methyl, triphenylmethyl, diphenylmethyl, benzyloxymethyl, C 3-6 - alkanoyloxymethyl, or phenacyl, are obtained by reacting an imino halide of the formula wherein X represents chlorine or bromine, R2B is the same as R2, C 2-4 -alkanoyl or a radical of the formula wherein each R3 independently represents C 1-4 alkyl or halogen, provided that at least one R3 represents C 1-4 alkyl; and R4 represents an acylamino group wherein the acyl group is C 1-4 alkanoyl, benzoyl, naphthoyl, C 2-5 -alkoxycarbonyl, C 6-7 - cycloalkoxy - carbonyl, phenoxycarbonyl, benzyloxycarbonyl, naphthyloxycarbonyl, one of the said groups substituted with from one to three groups selected from halogen, nitro, C 1-4 -alkoxy, cyano, and in the case of benzoyl, naphthoyl, benzyloxy, and naphthyloxy, by C 1-4 -alkyl, or phthaloyl, with an alcohol of the formula under essentially non-aqueous conditions. Those compounds wherein R‹ represents-CD 3 are claimed to be novel. The products may subsequently be reacted, optionally in situ, with a compound of one of the formulae or wherein X represents halogen and R5 represents C 1-8 alkanoyl, azidoacetyl, cyanoacetyl, haloacetyl, Ar-CH 2 -CO- where Ar denotes phenyl, thienyl, furyl, pyrrolyl, or phenyl substituted with from one to three substituents selected from halogen, trifluoromethyl, protected amino, protected hydroxy, C 1-3 alkyl, C 1-3 alkoxy, cyano and nitro, wherein Ar1 represents phenyl, pyridyl, or substituted phenyl as defined above, and Y is oxygen or sulphur, Ar-CH(B)-CO- wherein Ar is as defined above and B is protected amino, protected hydroxy, protected carboxy,-CN or - N 3 , 2-(3-sydnone)acetyl or 2-(1H-tetrazol-1- yl)acetyl. The starting materials of Formula