Application of Experimental Design (DoE) to Improve a Very Dilute Workup Procedure

IF 3.5 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2024-08-12 DOI:10.1021/acs.oprd.4c0019010.1021/acs.oprd.4c00190

Ekaterina Y. Melikhova, Dan A. Smith and Jonathan D. Moseley*,

引用次数: 0

Abstract

A three-level face-centered central composite experimental design was applied to the reaction parameters (concentration, stoichiometry, temperature) of an acid-catalyzed rearrangement of a morphine derivative, with the aim of reducing the very dilute workup procedure required for isolation of the aporphine product without compromising yield, quality, or other parameters. This enabled the concentration of starting material in the acid catalyst to be increased 2-fold while maintaining other parameters, resulting in nearly 60% overall volume reduction on workup. This formal experimental design study required only 17 tube-scale experiments, yielding a more robust process overall, and additionally provided a greater understanding of the reaction design space for potential future scale-up.

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应用实验设计（DoE）改进极稀释工作程序

对吗啡衍生物的酸催化重排反应参数（浓度、化学计量学、温度）进行了三级面心中心复合实验设计，目的是在不影响产率、质量或其他参数的情况下，减少分离阿朴啡产物所需的稀释处理过程。这样，在保持其他参数不变的情况下，酸催化剂中的起始原料浓度提高了 2 倍，从而使整个加样过程的体积减少了近 60%。这项正式的实验设计研究只需要进行 17 次试管规模的实验，因此总体工艺更加稳健，同时也让我们对反应设计空间有了更深入的了解，便于今后进行潜在的放大。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.