Synthesis of (5.R,10S,11R)-( + )-10,11-Dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10-imin-11-ol: A Hydroxylated Metabolite of MK-0801

Robert D. Larsen, Paul Davis, Edward G. Corley, Paul J. Reider, Theresa R. Lamanec, Edward J.J. Grabowski

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17 Scopus citations

Abstract

Two approaches to the synthesis of the MK-0801 metabolite, (5R,10S,11R)-(+)-10,11-dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10-imin-11-ol (1a), from dibenzosuberenone (2) are presented. Selective ring opening of an aziridine with acetyl bromide and inversion of the stereochemistry provide la. Alternatively, formation of an oxazolidinone ring at the 10,11-position of the suberenone via a bromohydrin (9) is followed by acid-catalyzed cyclization of the oxazolidinone-carbinol 12 to provide la. A practical resolution for obtaining the active 5R,1OS,11R-(+) enantiomer is described.

Original languageEnglish (US)
Pages (from-to)299-304
Number of pages6
JournalJournal of Organic Chemistry
Volume55
Issue number1
DOIs
StatePublished - Jan 1990
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

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