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

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.