Abstract Penicillin sulfoxides are converted to 3-halo-3-methyl-cepham-4-carboxylic acid esters and amides or the corresponding cephem derivatives by heating the penicillin sulfoxide precursor in a polyhaloalkane solvent to a temperature between 50° to about 150°C. in the presence of an equimolar amount of a neutral or basic catalyst, respectively. The catalysts employed are bases such as pyridine, picoline, lutidine, quinoline, isoquinoline, dimethylaniline or a quaternary ammonium salt. The 3-halo-cepham intermediates produced with a quaternary ammonium catalyst are dehydrohalogenated to afford known cephem derivatives or converted to the free 4-carboxylic acid and the alkali metal, alkaline earth metal or ammonium salts thereof to afford novel antibacterial agents.
A compound of the formula: ##SPC7## in which R 3 is a member selected from the group consisting of hydroxy, lower alkoxy, 2,2,2-trichloroethoxy, aryloxy of 6 to 10 carbon atoms, aralkoxy of 7 to 12 carbon atoms, alkoxyaralkoxy of 9 to 14 carbon atoms, mono- or di-lower alkylamino, arylamino of 6 to 10 carbon atoms, saccarimido, phthalimido, and OM where M is an alkali metal cation, an alkaline earth metal cation or the ammonium cation; A is a member selected from the group consisting of --Cl, --Br and --I; and the pharmaceutically acceptable acid addition salts thereof.
Claim 2
Dependent Claim
97 words
A compound of the formula: ##SPC7## in which R 3 is a member selected from the group consisting of hydroxy, lower alkoxy, 2,2,2-trichloroethoxy, aryloxy of 6 to 10 carbon atoms, aralkoxy of 7 to 12 carbon atoms, alkoxyaralkoxy of 9 to 14 carbon atoms, mono- or di-lower alkylamino, arylamino of 6 to 10 carbon atoms, saccarimido, phthalimido, and OM where M is an alkali metal cation, an alkaline earth metal cation or the ammonium cation; A is a member selected from the group consisting of --Cl, --Br and --I; and the pharmaceutically acceptable acid addition salts thereof.
Claim 3
Dependent Claim
11 words
The compound of claim 1 which is 7-amino-3-chloro-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]octane-2-carboxylic acid, p-nitrobenzyl ester.