Eli Lilly and Company

William B Blanchard

Charles W Ryan

Thomas Charles Britton

David Lee Varie

The present invention provides an enantiomerically selective process and intermediates for preparing certain 4,5-disubstituted pyrazolidinones and intermediates which are useful for treating diseases of the central nervous system.

Substituted pyrazolidin-3-one derivatives

Pyrazolidin-3-one derivatives

Superior method for the removal of the methyl or ethyl ester group from cephalosporin and carbacephalosporin carboxylic acids.

Process for cleavage of esters during the production of cephalosporins

Reaction of a 5-substituted resorcinol with a ketal of 4-(1-hydroxy)-1-methylethyl)-3-cyclohexen-1-one in the presence of a suitable catalyst effects condensation to provide substantially exclusively a cis-1-hydroxy-3-substituted-6,6-dimethyl-6,6a,7,8,10,10a-hexahydro-9H-dibe nzo[b,d]pyran-9-one.

Preparation of

Reaction of a 5-substituted resorcinol with a ketal of 4-(1-hydroxy-1-methylethyl)-3-cyclohexen-1-one in the presence of a suitable catalyst effects condensation to provide substantially exclusively a cis-1-hydroxy-3-substituted-6,6-dimethyl-6,6a,7,8,10,10a-hexahydro-9H-dibe nzo-[b,d]pyran-9-one.

Reaction of a 5-substituted resorcinol with a ketal of 4-(1-hydroxy-1-methylethyl)-3-cyclohexen-1-one in the presence of a suitable catalyst effects condensation to provide substantially exclusively a cis-1-hydroxy-3-substituted-6-6-dimethyl-6,6a,7,8,10,10a-hexahydro-9H-dibe nzo[b,d]pyran-9-one.

Reaction of an aluminum halide with a 2,7-dihydroxy-5-isopropylidene-9-substituted-2,6-methano-3,4,5,6-tetrahydr o-2H-1-benzoxocin in an organic solvent effects cleavage of the pyran ring system with concomitant recyclization to provide exclusively a trans-1-hydroxy-3-substituted-6,6-dimethyl-6,6a,7,8,10,10a-hexahydro-9H-di benzo[b,d]pyran-9-one.

Process for converting

Reaction of cis-1-hydroxy-3-substituted-6,6-dimethyl-6,6a,7,8,10,10a-hexahydro-9H-dibe nzo[b,d]pyran-9-ones with an aluminum halide in an unreactive organic solvent effects complete epimerization to provide the corresponding trans-1-hydroxy-3-substituted-6,6-dimethyl-6,6a,7,8,10,10a-hexahydro-9H-di benzo[b,d]pyran-9-one.

Process for converting cis-hexahydrodibenzo[b,d]pyran-9-ones to

A 7-aminocephalosporin is acylated to a 7-acylamidocephalosporin by reaction with the pentachlorophenyl ester of sydnone-3-acetic acid or 1-tetrazoleacetic acid.

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Indianapolis, IN, United States of America

William B Blanchard