Dujon Noronha, Prashant B. Patil, Kishor More, Mohan Anand Chandavarkar and Sudhir Sawant*,
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引用次数: 0
Abstract
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.
期刊介绍:
The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools,process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.