IE33374L - 7-aminocephalosporanic acid - Google Patents

Abstract

1281172 Preparing 7-aminocephalosporanic acid ELI LILLY & CO 17 June 1969 [19 June 1968 (2)] 30674/69 Heading C2A 7-Aminocephalosporanic acid is prepared by a process of reacting cephalosporin C or a salt thereof with a nitrosating agent, a carbocyclic arenediazonium salt or a compound that provides positive halogen, at a temperature below 60‹ C. in a solvent, and hydrolysing the resulting intermediate to give the 7-aminocephalosporanic acid, in which process an alkylene oxide containing 2 to 4 carbon atoms or #-propiolactone is added to the reaction mixture to obtain the 7- aminocephalosporanic acid. The alkylene oxide or propiolactone may be added to the hydrolysed reaction mixture resulting from treatment of the intermediate with water and/or a C 1 -C 3 alkanol, in which case its function is to precipitate the 7-aminocephalosporanic acid (7-ACA). Alternatively it may be added to the residue left after evaporating the reaction solvent before hydrolysis, when hydrolysis is brought about without the use of water and/or alkanol and 7- ACA is precipitated directly on adding the alkylene oxide or propiolactone. The reaction solvent is preferably a mixture of formic acid and nitroalkane with or without acetonitrile. Excess of the nitrosating agent, arenediazonium salt or compound providing halogen is preferably destroyed after the reaction, e.g. by adding ammonium sulphamate. Suitable alkylene oxides are ethylene oxide (i.e. oxirane), 1,2- propylene oxide, butene-1-oxide and butene-2- oxide. They may be added in a solvent, preferably all at once, suitable solvents being acetonitrile, ketones, esters, dioxane and tetrahydrofuran, which are poor solvents for the 7-ACA. 3-30 moles of alkylene oxide per mole of cephalosporin C starting material are used. Reference has been directed by the Comptroller to Specification 948858. [GB1281172A]