Merck + Co., Inc.

University of California

Dean R Bender

Henry Rapoport

Ichiro Shinkai

Sandor Karady

John E Hearst

James A McCauley

Kevin Michael Belyk

David L Hughes

Regina M Black

William R Leonard

Theresa Rothauser

Anthony M De Marco

There is disclosed a novel process for preparing aza cyclohexapeptides of the formula ##STR1## where all variables are defined herein.

Process for preparing certain aza cyclohexapeptides

A process for isomerizing an alpha methylated azetidinone alkyl ester to the corresponding beta-methyl isomer, which is an intermediate in the synthesis of 1-beta-methylcarbapenem antibacterial agents. The process involves treating the dianion of structure I, being the alpha isomer, with a P-H or S-H containing organic protic acid, organometallic Sn or Pb hydride, metallic cation salt or trialkyl borane, followed by quenching with an OH protic organic acid or mineral acid.

Process for producing 1-beta-methylcarbapenem antibiotic intermediates

(+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine, and its pharmaceutically acceptable salts is useful as an anxiolytic, antidepressant, anticonvulsant, muscle relaxant and in the treatment of mixed anxiety-depression, minimal brain dysfunction and extrapyramidal disorders such as Parkinson's disease. The racemate of the compound is produced by a four-step synthetic process in about 65% yield from 5H-dibenzo[a,d]cyclohepten-5-one.

Process for 5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine

Two species of a coumarin derivative are disclosed, both of which may be produced from a 7-hydroxycoumarin precursor. The one species is an oxime and the other is a .beta.-haloallyl ester. A method for making a psoralen compound in high yield comprises treating these coumarin derivatives with an acid to fuse a furan ring thereto, and recovering a 5'-methyl psoralen therefrom. The 5'-methyl psoralen may be produced in up to about 70% overall yield with respect to the 7-hydroxycoumarin precursor.

Coumarin derivatives and method for synthesizing 5'-methyl psoralens

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Hazlet, NJ, United States of America

Dean R Bender