Method for preparation of .beta.-lactam compound
AssigneeFujisawa Pharmaceutical Co., Ltd.
InventorsTakao Takaya, Hiromu Kochi, Takashi Masugi
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Abstract
A process for preparing a 7-substituted-3-cephem-4-carboxylic acid of the formula: ##STR1## or a pharmaceutically acceptable salt thereof, which comprises subjecting a corresponding 7-substituted-3-organic sulfonyloxy-3-cephem-4-carboxylic acid ester of the formula ##STR2## wherein R is a residue of an organic sulfonic acid, X is esterified carboxy which is an alkoxylcarbonyl, haloalkoxycarbonyl, substituted or unsubstituted aralkoxycarbonyl, benzhydryloxycarbonyl or trityloxycarbonyl, or a pharmaceutically acceptable salt thereof, to hydrogenolysis using a combination of a metal and formic acid as a reducing reagent.
Claims11
A process for preparing a 7-substituted-3-cephem-4-carboxylic acid of the formula:
- ##STR8## or pharmaceutically acceptable salt thereof, which comprises:
- subjecting a solution of a corresponding 7-substituted-3-organic sulfonyloxy-3-cephem-4-carboxylic acid ester of the formula:
- ##STR9## wherein R is an organic sulfonyl moiety which is a residue of an organic sulfonic acid which is unsubstituted or halo or nitro substituted alkanesulfonyl or arenesulfonyl, X is an esterified carboxy which is convertible to carboxy by hydrogenolysis and is alkoxylcarbonyl, haloalkoxycarbonyl, aralkoxycarbonyl, benzhydryloxycarbonyl, trityloxycarbonyl, 4-nitrobenzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, 4-hydroxy-3,5-di(tert)butylbenzyloxycarbonyl, or a pharmaceutically acceptable salt of compound I, to hydrogenolysis of the -OR moiety and of the esterified carboxy X by means of a reducing reagent which is iron, zinc or tin in admixture with formic acid, wherein each of A.sub.1 and A.sub.2 is a substituent in the 7-cephem position selected from the group consisting of amine, an acylamino, or a protected amino in which the protecting group is an easily removable protecting group other than an acyl group, and wherein the acyl moiety of said acylamino is selected from alkanoyl, cycloalkanecarbonyl, alkenoyl, aroyl, alkoxycarbonyl, adamaotyloxycarbonyl, aryloxycarbonyl, alkanesulfonyl, arenesulfonyl, 8-quinolyloxycarbonyl, pyridyloxycarbonyl, thenoyl, furoyl, nicotinoyl, isonicotinoyl, arylcarbamoyl, alkylcarbamoyl, alkylthiocarbamoyl, phenylthiocarbamoyl, tritylthiocarbamoyl, succinyl, fumaroyl, phthaloyl, aroylalkanoyl, haloalkanoyl, cyanoalkanoyl, cycloalkylalkanoyl, alkoxyalkanoyl, alkylthioalkanoyl, alkoxycarbonylalkanoyl, aralkanoyl, ar(amino)alkanoyl, ar(hydroxy)alkanoyl, aryl(alkanoyloxy)alkanoyl, aryloxyalkanoyl, ((alkoxy, nitro, or halo)aryloxy)alkanoyl, 2-nitro-4-chlorophenoxyacetyl, arylthioalkanoyl, nitroarylthioalkanoyl, chloroarylthioalkanoyl, thienylacetyl, thiadiazolylacetyl, thiazolylacetyl, tetrazolylacetyl, pyridylacetyl, thienylpropionyl, benzothiazolon-3-ylacetyl, oxadiazolyacetyl, methylthaizolylacetyl, aminothazolylacetyl, pyridyloxyacetyl, pyridylthioacetyl, thiadiazolylthioacetyl, aralkenoyl, (nitro,halo, alkanesulfonyl, hydroxy, alkanesulfonamido, alkanoylamino, alkoxy, alkoxycarbonyl or cyano) aroyl, 2-hydroxy-5-chlorobenzoyl, haloalkoxycarbonyl, 2-pyridylmehtoxycarbonyl, cycloalkyloxycarbonyl, aralkoxycarbonyl, (halo, nitro, alkoxy or phenylazo) aralkoxycarbonyl, haloaryloxycarbonyl, or haloalkylcarbamoyl.
Dependencies are inferred from the claim text.