伯沙卡帕韦的工艺开发，第3部分：与卤仿型酰胺生成氯仿相关的安全性和后期开发考虑

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

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引用次数: 0

摘要

这篇手稿描述了合成一种关键酰胺中间体的化学过程的发展，以及在以前的过程中所取得的改进。在蒸馏模型的指导下进行的仔细研究揭示了与连续体积相比，放取操作的优势，并导致离散蒸馏值成功捕获馏出物中的CHCl3，然后可以单独处理。优化了作业条件和结晶，提高了收率，简化了废物处理。该工艺是稳健的，并已成功地扩大了多个生产活动。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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

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

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.