GB1265332A - - Google Patents

Abstract

1,265,332. #<SP>2</SP>-Cephalosporins. ELI LILLEY & CO. 7 Feb., 1969 [7 Feb., 1968; 13 Jan., 1969 (2)], No. 6824/69. Heading C2A. Novel #<SP>2</SP>-cephalosporins of Formula I wherein R is trimethylsilyl, triphenylmethyl, butoxycarbonyl, phenoxyacetyl, phenylacetyl, phenylmercaptoacetyl or phenyl-α,α-dimethylacetyl, or a phenoxyacetyl, phenylacetyl, phenylmercaptoacetyl or phenyl - α,α - dimethylacetyl group ring substituted with F, Cl, Br, I, NO 2 , CN, CF 3 , C 1 to C 6 alkyl, C 1 to C 2 alkoxy or butoxycarbonylmethyl; R<SP>11</SP> is CN or XY where X is O or S and Y is C 1 to C 10 alkyl, C 3 to C 10 alkenyl, C 3 to C 15 alkynyl, C 5 to C 7 cycloalkyl, C 3 to C 6 cycloalkyl-C 1 to C 6 alkyl, C 2 to C 10 haloalkyl, C 3 to C 10 haloalkenyl, C 3 to C 10 haloalkynyl, C 1 to C 3 cyanoalkyl, C 1 to C 3 alkyl-X-C 1 to C 6 alkyl where X is O or S, C 1 to C 6 alkoxycarbonyl-C 1 to C 6 alkyl, C 2 to C 4 alkanoyl-C 1 to C 6 alkyl, C 2 to C 4 alkanoyloxy- C 1 -C 6 alkyl, (2<SP>1</SP>-tetrahydrofuryl)-C 1 to C 3 alkyl, 31-tetrahydrofuryl, (2<SP>1</SP>-thienyl)-C 1 to C 3 alkyl, phenyl-C 1 to C 3 alkyl, or a phenyl, benzyl or phenethyl group which may be substituted with CN, NO 2 , CF 3 , C 1 to C 3 alkyl, C 1 to C 3 alkoxy or C 1 to C 3 alkoxycarbonyl, or R<SP>11</SP> is where R<SP>3</SP> and R<SP>4</SP> are each C 1 to C 6 alkyl or together with the common N atom complete a 5 to 6 ring atom-containing heterocycle of formula in which n is 0 or 1 and Q is -CH 2 -, -O-, -S- or where R<SP>6</SP> is H or C 1 to C 4 alkyl, except that when n is 0, Q is -CH 2 -; and R<SP>1</SP> is C 4 to C 6 tert. alkyl, C 5 to C 7 tert. alkynyl, benzyl, methoxybenzyl, nitrobenzyl, phenacyl, trimethylsilyl, benzhydryl, phthalimidomethyl or succinimidomethyl, are prepared by reacting N-bromosuccinimide with a 3-desacetoxy-#<SP>2</SP>-cephalosporin of Formula III in an anhydrous organic solvent at about 40‹ to 100‹ C. to give a novel 3-bromomethyl-#<SP>2</SP>- cephalosporin of Formula IV which compound is then reacted with an appropriate nucleophilic reagent to replace the bromine atom by the group R<SP>11</SP>. The starting cephalosporins III may be prepared by hydrogenating a #<SP>3</SP>-cephalosporin ester to form the corresponding #<SP>3</SP>-desacetoxycephalosporin ester which is treated with a base such as pyridine in the cold to isomerize the #<SP>3</SP> double bond to the #<SP>2</SP> position. In addition to the #<SP>2</SP> compounds of Formula I, the inventive process may form some of the corresponding #<SP>3</SP> cephalosporins due to the basic conditions which may be used in the nucleophilic displacement of the Br atom. Alternatively the #<SP>2</SP> compounds may be converted to corresponding #<SP>3</SP> compounds by oxidation to the #<SP>3</SP> sulphoxide which is subsequently reduced, according to Specification 1,265,333.