An approach to the synthesis of (±)-(1R,6R,7R)-2-azabicyclo4.2.0octan-7-ol, a promising amino alcohol building block for drug discovery, has been described. The method is based on 2+2 the cycloaddition of tert-butyl vinyl ether and a ketene generated in situ from a glutaric acid derivative, as well as the intramolecular lactam formation as the key steps. Although the 2+2 cycloaddition step and further transformations proceeded without any notable stereoselectivity, the title compound was synthesized in an amount greater than 30 g with a high diastereomeric purity. This was provided by the physical properties of the intermediate (±)-(1R,6R,7R)-7-(tert-butoxy)-2-azabicyclo4.2.0octan-3-one that was easily separated by crystallization.
Nosyk et al. (Fri,) studied this question.