New approach to the rac-(3R,6aS,11aS)-2-methyl-1,3,4,5,6,11a-hexahydro-2H-3,6a-methanobenzofuro[2,3-c]azocine-8-ol (c-oxide-bridged phenylmorphan)

ORGN 730

Jin-Hee Kim, jheeeee@gmail.com1, Jeffrey R. Deschamps2, Arthur E. Jacobson, aej@helix.nih.gov1, and Kenner C. Rice, kr21f@nih.gov1. (1) Drug Design and Synthesis Section, Chemical Biology Research Branch, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institute of Health, DHHS, 5625 Fishers Lane, Room 4N03, MSC 9415, Rockville, MD 20852, (2) Laboratory for the Structure of Matter, Naval Research Laboratory, Washington, DC 20375
rac-2-Benzyl-4-bromo-5-(2,3-dimethoxyphenyl)- 2-azabicyclo[3.3.1]nonane (1), synthesized as previously reported, was used to prepare the benzoate ester derivative, reversing the stereochemistry at C-4 from the axially oriented C-4 bromo to the equatorially oriented OBz moiety. The ester was hydrolyzed to afford the desired equatorially oriented hydroxy compound at C-4 that was mesylated to the key intermediate. Ring closure gave the needed N-methyl ortho c-oxide bridged phenylmorphan and that compound was converted to the new N-phenethyl substituted ortho-c compound (2).