Process Development of Bersacapavir, Part 3: Safety and Late-Stage Development Considerations Linked to Chloroform Generated in Haloform-Type Amidation

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED Organic Process Research & Development Pub Date : 2025-03-04 DOI:10.1021/acs.oprd.4c00516

David Kossler, Micha Peeters, Florian Medina, Erika De Bie, Brecht Egle, Cheng Cheng Huang, William M. Maton, Johan Weerts, Jean-Pierre Bongartz, Magnus Eriksson, Koen Wegsteen, Els Keppens

引用次数: 0

Abstract

This manuscript describes the chemical process development for the synthesis of a crucial amide intermediate and the improvements that were achieved over previous processes. Careful studies guided by distillation modeling revealed an advantage of put-and-take operation compared to continuous volume and led to the discrete distillation values to successfully capture CHCl₃ in the distillate, which can then be disposed of separately. Optimization of the workup conditions and crystallization resulted in higher yields and simplified waste treatment. The process is robust and has been successfully scaled up in multiple production campaigns.

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来源期刊

Organic Process Research & Development 化学-应用化学

CiteScore

6.90

自引率

14.70%

发文量

251

审稿时长

2 months

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.