Process for the Preparation of Beta-Amino Alcohol

摘要

A high-yielding enantioselective synthesis of the bioactive (S)—N-(5-chlorothiophene-2-sulfonyl)-β,β-diethylalaniol (7.b.2), a Notch-1-sparingγ-secretase inhibitor metabolite (with EC50=28 nM) effective in reduction of Aβproduction in vivo, has been realized starting from readily available 3-pentanone. The key steps of the synthesis are proline-catalyzedα-aminooxylation andα-amination of aldehyde; the latter contributing an overall yield of 50-75% and 90-99% enantiomeric excess.