AN IMPROVED PREPARATION OF 2-AZABICYCLO[2.2.2]OCTANE

ABSTRACT

An improved preparative four-step synthesis to isoquinuclidine tosylate salt 4 has been demonstrated in 70% overall yield from p-aminobenzoic acid (PABA) 1. Hydrogenation of PABA 1 affords 4-aminocyclohexane carboxylic acid 2 as an 80 : 20 mixture of cis- and trans-isomers. Heating the mixture at 250°C effected epimerization and cyclization to provide the bicyclic lactam 3. Subsequent Red-Al reduction and treatment with tosic acid furnished the desired bicyclic amine, tosylate salt 4.

Keywords:

• Bicyclic aza compounds
• Hydrogenation
• Lactamisation
• Reduction

ACKNOWLEDGMENTS

We thank Drs. Li Li, Thomas Dowling, and Ms. Lisa DiMichele for their help with the analytical assays and NMR studies.