Validation of a purity method for a Suzuki-Miyaura boronic ester by liquid chromatography with derivatization

The Miyaura borylation reaction enables the direct synthesis of boronates, a valuable partner in Suzuki-Miyaura coupling reactions. These C-C coupling reactions provide one of the most efficient methods for the construction of C-C bonds and are widely used in transition metal-catalyzed organic chemistry. However, analyses of these boronic acid/ester products and their derivatives are rarely discussed. In this communication, a sensitive and selective liquid chromatography method has been validated for the purity determination of a boronic ester intermediate where significant sample preparation challenges were observed. An efficient in-situ derivatization was implemented which consisted of a hydrolysis to the boronic acid derivative while simultaneously poisoning any residual active palladium. The HPLC analysis was performed on an Zorbax XDB-C18 (150 mm x 4.6 mm) 3.5 µm column utilizing water/acetonitrile gradient elution with an acidic modifier of 0.5 % trifluoroacetic acid at a flow rate of 1.0 mL/min. The detection was performed at the wavelength of 254 nm, and the retention time of the boronic ester was around 4.9 min. The proposed method was validated to ICH Q2 standards and included such parameters as specificity, system precision, accuracy/reproducibility, linearity, LOD/LOQ and solution stability.