Knowledge Center

Article / 2019

Optimization of Monofluoromethylation Reagents

Synthesis of Pharmaceutical Steroids as a Case Study

Authors:
  • Emilia Leitao
Source:
American Pharmaceutical Review, 14 May 2019

The efficient and selective incorporation of monofluoromethyl groups into organic molecules has attracted great attention in recent years. Monofluoromethylation is usually archived by direct functionalization with CH2FBr or indirectly, via CH2BrI, CH2ClI, or similar agents. These reagents are ozone depleting substances and its use should be strictly avoided. In this work, we successfully optimized the conditions to prepare fluoromethyl phenyl sulfoxide, a key intermediate in the preparation of monofluoromethylating reagents. A protocol to perform the monofluoromethylation of two steroids was also developed, which was validate through the synthesis of two important and complex pharmaceutical drugs used in the treatment of asthma and rhinitis, fluticasone propionate and fluticasone furoate, respectively.

Read the entire eBook: Small Molecule Development - Analytical Methods for Faster Time to Market