Synthesis of a <i>cis</i> 2,5-Disubstituted Morpholine by De-epimerization: Application to the Multigram Scale Synthesis of a Mineralocorticoid Antagonist

A convergent route to multigram quantities of a mineralocorticoid antagonist <b>3</b> is described. Starting from (<i>R</i>)-phenylglycinol, the synthesis of <i>cis</i> 2,5-morpholine <b>2</b> is accomplished utilizing a de-epimerization to install the second stereogenic center. The multigram synthesis of <b>3</b> was completed through a sequence of an S_NAr reaction, Dakin oxidation, alkylation, and cyclization to provide a crystalline solid