Asymmetric Synthesis of the Carbon-14-Labeled Selective Glucocorticoid Receptor Modulator using Cinchona Alkaloid Catalyzed Addition of 6-Bromoindole to Ethyl Trifluoropyruvate

Abstract

We describe in this study the asymmetric synthesis of radioisotope (RI)-labeled selective glucocorticoid receptor modulator. This synthesis is based on optimization of the cinchona alkaloid catalyzed addition of 6-bromoindole to ethyl trifluoropyruvate and Negishi coupling of zinc cyanide to the 6-bromoindole moiety. [¹⁴C] Labeled (−)-{4-[(1-{2-[6-cyano-1-(cyclohexylmethyl)-1<em>H</em>-indol-3-yl]-3,3,3-trifluoro-2-hydroxypropyl}piperidin-4-yl)oxy]-3-methoxyphenyl}acetic acid (−)-<strong>1</strong> was synthesized successfully with high enantioselectivity ( > 99% <em>ee</em>) and sufficient radiochemical purity.

Keywords

• organocatalyst
• cinchona alkaloid
• asymmetric synthesis
• radioisotope labeled compound