6-Azabicyclo[3.2.1]octane derivatives: Synthesis of the 8,12-methanoazepino[2,1-a]isoquinoline system

Abstract

The synthesis of the 8,12-methanoazepino[2,1-a]isoquinoline system 1 by Bischler-Napieralski cyclization of an appropriate 6-phenethyl-6-azabicyclo[3.2.1]octan-7-one derivative 2 is described. Lactam 2 was prepared by three alternative procedures: (a) direct alkylation of normorphan 6 , (b) alkylation of lactim ether 7 with 3,4,5-trimethoxyphenacyl bromide followed by NaBH 4 reduction and hydrogenolysis, and (c) lactamization of amino esters 11 or 13 , which were obtained from ethyl or methyl 3-aminocyclohexanecarboxylate by direct alkylation or by acylation with 3,4,5-trimethoxyphenylacetyl chloride and further diborane reduction, respectively.