Belzutifan的制造工艺开发，第5部分:流线型氟化-动态动力学分辨工艺

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED Organic Process Research & Development Pub Date : 2021-11-15 DOI:10.1021/acs.oprd.1c00242

Tao Wang*, Eric M. Phillips*, Stephen M. Dalby, Eric Sirota, Stephanus Axnanda, C. Scott Shultz, Pratiq Patel, Jacob H. Waldman, Embarek Alwedi, Xiao Wang, Kerstin Zawatzky, Matthew Chow, Nilusha Padivitage, Mark Weisel, Michael Whittington, Jianjun Duan, Taotao Lu

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引用次数: 9

摘要

本文报道了商业供应的别祖替芬(MK-6482)的氟化-动态动力学解析(DKR)过程。在增加机理理解的基础上，确定并解决了选择氟氟化反应中的关键工艺安全性和稳健性问题。积极的工艺优化实现了单罐直接分离工艺，允许以低工艺质量强度交付氟二醇产品。

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Manufacturing Process Development for Belzutifan, Part 5: A Streamlined Fluorination–Dynamic Kinetic Resolution Process

Here we report the fluorination–dynamic kinetic resolution (DKR) process for the commercial supply of belzutifan (MK-6482). Key process safety and robustness issues in the Selectfluor fluorination reaction were identified and addressed on the basis of increased mechanistic understanding. Aggressive process optimization enabled a single-pot direct isolation process that allowed delivery of the fluorodiol product with low process mass intensity.

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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.