A short synthesis of 1-azaadamantan-4-one and the 4r and 4s isomers of 4-amino-1-azaadamantane

Article abstract of DOI:10.1055/s-1992-26307

Reductive homologation of 1,4-cyclohexanedione monoethylene acetal (1) with tosylmethylisocyanide and subsequent reduction with lithium aluminum hydride gave 1,4-dioxaspiro[4.5]decan-8-yl-methylamine (3) which was converted to 1-azatricyclo[3.3.1.1^3,7] decan-4-one (4) via a known double-Mannich condensation. Reductive amination of this ketone gave the corresponding 1-azatricyclo[3.3.1.1^3,7]decan-4 (s and r)-amines (9 and 10) which were separated on a multigram scale as their corresponding tosylamides 7 and 8, followed by deprotection.