KINETIC-ANALYSIS AND SUBAMBIENT TEMPERATURE CHROMATOGRAPHY OF AN ACTIVE ESTER

The inherent instability of active esters provides a chromatographic c hallenge. A normal phase HPLC gradient was developed using nonprotic s olvents and a diol stationary phase to determine the impurity profile of a mesylate which, under protic conditions, undergoes intramolecular ring closure to a cyclic ether. On-column cyclization of the analyte was found to be extensive at room temperature but insignificant at -30 degrees C. The on-column reaction rate was determined as a function o f column temperature, and an Arrhenius activation energy was calculate d.