Case Studies on Enabling Data-Rich, Parallelized Kinetic Analysis for Process Optimization with the ReactALL Platform

IF 3.3 3区 化学 Q2 CHEMISTRY, APPLIED
Organic Process Research & Development Pub Date : 2026-07-17 Epub Date: 2026-06-30 DOI:10.1021/acs.oprd.6c00131
Vaishnavi N. Nair, Andreas R. Rötheli, Alan H. Cherney, Madeleine C. Deem, Melodie Christensen, Kevin Stone, Lu Han, Sebastien Monfette* and Truong N. Nguyen*, 
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Abstract

Automated, scale-predictive reaction profiling is often constrained by material limitations, sampling fidelity, and/or reactor mixing artifacts. We report the application of ReactALL, a five-reactor automated platform with a 5 mL working volume that integrates overhead agitation with built-in sampling, to generate reproducible, data-rich time-course reaction profiles. The performance of ReactALL was validated through three industry-relevant case studies: (1) the rapid, material-efficient development of an amidation reaction (Sanofi), (2) variable time normalization analysis (VTNA) of a Pd-catalyzed Suzuki–Miyaura coupling reaction (MSD), and (3) kinetic modeling of an SNAr reaction (Pfizer). In each case, data sets obtained from ReactALL closely matched those obtained from established laboratory reactors while offering >10-fold savings in material consumption compared to conventional automated laboratory reactors. The analysis of the generated data provided valuable and actionable insights into reaction behavior, accelerating effective process optimization and predictive modeling across a range of reaction types. Collectively, these results demonstrate that ReactALL enables material-efficient, parallelized generation of high-quality kinetic data, supporting mechanistic analysis, predictive modeling, and scalable process development.

Abstract Image

利用ReactALL平台实现富数据、并行化动力学分析的过程优化案例研究
自动化的、规模预测的反应分析通常受到材料限制、采样保真度和/或反应器混合工件的限制。我们报告了ReactALL的应用,这是一个5个反应器的自动化平台,工作体积为5ml,集成了架空搅拌和内置采样,以生成可重复的,数据丰富的时间过程反应曲线。ReactALL的性能通过三个与行业相关的案例研究得到验证:(1)快速、高效地开发酰胺化反应(赛诺菲),(2)pd催化的Suzuki-Miyaura偶联反应(MSD)的变时间归一化分析(VTNA),以及(3)SNAr反应的动力学建模(辉瑞)。在每种情况下,从ReactALL获得的数据集与从现有实验室反应堆获得的数据集非常匹配,同时与传统的自动化实验室反应堆相比,材料消耗节省了10倍。对生成数据的分析为反应行为提供了有价值且可操作的见解,加速了有效的流程优化和一系列反应类型的预测建模。总的来说,这些结果表明,ReactALL能够高效地、并行地生成高质量的动力学数据,支持机制分析、预测建模和可扩展的过程开发。
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来源期刊
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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