Basic Information
Poster Number: 860-6    
Author Name: Megan Sun Affiliation: Genentech
Session Title: Pharmaceutical LC, HILIC and GPC I
Event Type: Poster
Event Title: A General HPLC Method for the Analysis of Pinacol Esters with Conjugated Chemical Features
Presider(s):   Start Time: ( Slot # 6 )
Date: Monday, March 12th, 2012 Location: Red Area on Exposition Floor, Aisles 1300-1500
Keywords: Analysis, Characterization, Chromatography, HPLC

Co-Authors
NameAffiliation
Li, JaneGenentech
Ngim, KenGenentech
Zhong, QiqingGenentech

Abstract Content
Pinacol esters have been widely used as the reactants with core moiety through Suzuki Coupling reactions in the synthesis of active pharmaceutical ingredients (API). Under either acidic or neutral aqueous condition, these esters are prone to lose the protective ester group and convert to the corresponding boronic acids. Because of this unstable nature, it is an analytical challenge to develop HPLC methods using water-based mobile phases for pinacol esters. Here a reversed phase HPLC method was described and shown to be generally applicable for the analysis of pinacol esters with R-electron rich chemical features. The method employed a PLRP-S column (4.6x150mm, 3µm), a styrene divinyl benzene copolymer column from Agilent Technologies, and basic aqueous mobile phases. Samples were prepared in anhydrous organic solvents DCM/DMF (50/50) or DCM/ACN (50/50) to minimize the hydrolysis of the esters. To better understand the retention mechanism of the column, a number of commercially available or internally prepared pinacol esters that contain R-electron features in their structures were evaluated with this LC method. All test compounds retained well on the column with good chromatography and showed minimal degradation to form their corresponding boronic acids under the method conditions. It was therefore concluded that R-R interaction between the PLRP-S column and the test molecule is the main driving force for retention. In addition, resolution of positional isomers was achieved using this method for pinacol esters with conjugated chemical structures. This method also allowed the simultaneous detection of pinacol esters and their corresponding boronic acids due to their significant hydrophobicity difference.