A practical synthesis of Cbz protected (1R,2R) and (1S,2S) 2-hydroxy-cyclobutylamines

Abstract

(1R,2R) and (1S,2S) 2-hydroxy-cyclobutylamines are important substructures in a range of bio-active molecules and pharmaceutical candidates. In view of the potential safety issues and the low reaction efficiency associated with the earlier published synthetic process, which relies on Curtius rearrangement for the synthesis of 2-amino-cyclobutanone intermediate, a more practical and efficient process to prepare (1R,2R) and (1S,2S) 2-hydroxy-cyclobutylamines using readily available N-Cbz-2-amino-cyclobutanone was developed. Cbz protected (1R,2R) 2-hydroxy-cyclobutylamine could be synthesized in 14 % yield over 5 steps.