IE33460L - 7-aminocephalosporanic acid - Google Patents

Abstract

1,270,955. Preparing 7-aminocephalosporanic acid. ELI LILLY & CO. 17 June, 1969 [19 June, 1968], No. 30581/69. Heading C2A. 7-Aminocephalosporanic acid (7-ACA) is prepared by reacting cephalosporin C with a nitrosating agent, a carbocyclic arenediazonium salt or a compound that provides positive halogen, in a solvent at not more than 60‹C., and destroying excess of the said agent, salt or compound by adding a compound of formula: MSO 3 NH 2 , (sulphamates); YSO 2 NH 2 , (sulphamides); YSO 2 NHNH 2 , (sulphonylhydrazides); (semicarbazides and thiosemicarbazides); (carbazides and thiocarbazides); (thioureas); (carbamates and thiocarbamates); (carbazates and thiocarbazates); R 2 N-NH 2 , (hydrazines); (hydrazides and thiohydrazides); or Z 2 -C=CHZ, (unsaturated hydrocarbons), wherein M is H, NR 4 or alkali metal; X is O or S; Y is R or NR 2 , Z alone is R or or two Zs together with their attached carbons form a C 5 to C 6 ring; R is H, C 1 to C 6 alkyl, or C 6 to C 12 aryl or aralkyl; and R<SP>1</SP> is C 1 to C 6 alkyl or C 6 to C 12 aryl or aralkyl; then evaporating the solvent from the reaction mixture to leave a residue; subjecting the residue to hydrolytic cleavage to yield 7-ACA and recovering the 7-ACA. Preferably the excess of the nitrosating agent, diazonium salt or halogen-providing compound is destroyed using one of the listed compounds together with an acid such as H 2 SO 4 , oxalic, toluenesulphonic, trifluoroacetic, trichloroacetic, methane-sulphonic or phosphoric acid. In a preferred process the cephalosporin C is treated with nitrosyl chloride in formic acid and acetonitrile at - 10‹ to + 5‹ C., excess nitrosyl chloride is destroyed with ammonium sulphamate, the residue after evaporating the solvents is dissolved in water, brought to pH 3À5 and the precipitated 7-ACA is collected. [GB1270955A]