Chiral Supercritical Fluid Chromatography in the Preparation of Enantiomerically Pure (S)-(+)-tert-Butyl-3-hydroxyazepane-1-carboxylate

We report herein the isolation and characterization of (S)-(+)-tert-butyl-3-hydroxyazepane-1-carboxylate via resolution of the commercially available racemate, using chiral supercritical fluid chromatography (SFC). After optimization of the experimental chromatographic conditions, preparative scale separation using a stacked injections protocol led to 10.5 g of the dextrogyre enantiomer. Assignment of the absolute stereochemistry of the latter was accomplished by transforming (−)-tert-butyl-3-hydroxyazepane-1-carboxylate into known (R)-(−)-benzyl-3-hydroxyazepane-1-carboxylate.