An Improved and Scalable Process for Obtaining Pure Betaxolol Hydrochloride on an Industrial Scale

This study details the development of a novel and improved process for the multikilogram scale synthesis of Betaxolol hydrochloride, a β-blocker medication. The condensation of cyclopropyl methyl bromide (CPMBr) with a phenylethanol intermediate to produce an oxirane intermediate was a vital step in the synthesis. The reaction with isopropyl amine then produced a racemate of the Betaxolol base. The purification of crude Betaxolol base via sorbate salt formation and its crystallization enabled the desired quality of the Betaxolol base. It aided in achieving the desired quality in accordance with International Conference on Harmonization (ICH) guidelines and specification requirements outlined in the European Pharmacopoeia (EP) monograph. This improved process eliminated the need for column chromatography. There were only a few process impurities in the intermediates. The new approach described here is more efficient, with an overall yield of 37% with a quality of 99.8%, and sustainable than earlier processes reported in the literature, and it has the potential to become the commercial manufacturing route. This process was used to produce Betaxolol hydrochloride on a 20 kg scale without column chromatographic purification from para-hydroxy phenyl ethanol as the starting material and submitted to a Certificate of Suitability (CoS) with a regulatory authority.