Investigations into the alkaline instability of 7α-hydroxy metabolites of tipredane

Abstract

The instability of the rodent metabolites of tipredane towards sodium hydroxide has been investigated. The major degradant has been characterized as a 9-, 11β-epoxide and represents the first reported case of the elimination of hydrogen fluoride from 9α-fluoro, 11β-hydroxy substituted steroids. The 7α-hydroxy moiety in these metabolites has been shown to promote the hydrogen fluoride elimination reaction in the presence of sodium hydroxide. The rate of hydrogen fluoride elimination versus dehydration of the 7α-hydroxy substituent has been shown to be influenced by the sodium hydroxide concentration and the solvent composition.