Solving Gas–Liquid Mixing-Induced Clogging in Continuous-Flow Hydrogenation Synthesis of an API Intermediate

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED Organic Process Research & Development Pub Date : 2024-10-21 DOI:10.1021/acs.oprd.4c0032410.1021/acs.oprd.4c00324

Jadid E. Samad*, Douglas Connolly, Zheng Zhao and Joel M. Hawkins,

引用次数: 0

Abstract

A simple and widely applicable technique to avoid precipitation-induced clogging in continuous-flow processes involving gas and liquid reagents (such as hydrogenations) has been developed. Management of solid compounds poses one of the largest scale-up risks in the flow manufacturing of pharmaceuticals and fine chemicals. As noted in this study, compounds with limited solubility in low-boiling solvents can be susceptible to precipitation when mixed with a gas stream in a standard tee-mixer. The prescribed technique, whereby the gas stream is prewetted with a solvent prior to contacting with the feed solution, has been successfully applied both in lab and scale-up platforms to enhance the stable (clog-free) operating run time of continuous-flow synthesis of an active pharmaceutical ingredient (API) intermediate from minutes to days.

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解决连续流加氢合成原料药中间体过程中气液混合引发的堵塞问题

在涉及气体和液体试剂（如氢化）的连续流工艺中，开发了一种简单而广泛适用的技术来避免沉淀引起的堵塞。固体化合物的管理是药品和精细化学品流动生产过程中最大的放大风险之一。正如本研究中所指出的，在低沸点溶剂中溶解度有限的化合物在标准三通混合器中与气流混合时容易发生沉淀。规定的技术，即在气流与进料溶液接触前用溶剂预湿，已成功应用于实验室和放大平台，将活性药物成分 (API) 中间体连续流合成的稳定（无堵塞）运行时间从几分钟延长到几天。

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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.

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