Synthesis of (5R,10S,11R)-(+)-10,11-Dihydro-5-methyl-5H-dibenzocyclohepten-5,10-imin-11-ol: A Hydroxylated Metabolite of MK-0801

Article abstract of DOI:10.1021/jo00288a050

Two approaches to the synthesis of the MK-0801 metabolite, (5R,10S,11R)-(+)-10,11-dihydro-5-methyl-5H-dibenzocyclohepten-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 1a.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 1a.A practical resolution for obtaining the active 5R,10S,11R-(+) enantiomer is described.