Streamlined Isolation of Magnesium Aryl Sulfinate Enabled by the Hydration of Sulfinate Salt to Magnesium Tetrahydrate

IF 3.5 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2025-06-28 DOI:10.1021/acs.oprd.4c00538

Heng Chen*, Aaron C. Spahr, Alan J. Shaffer, Rebecca J. W. Beck and Todd W. Koretke,

引用次数: 0

Abstract

A streamlined isolation of a magnesium aryl sulfinate tetrahydrate salt was enabled by the interplay of hydration and solubility. We discovered that the addition of a small amount of water at the end of the reaction between arylmagnesium bromide and 1,4-diazabicyclo[2.2.2]octane sulfur dioxide (DABSO) led to precipitation of a bench-stable magnesium aryl sulfinate salt in its tetrahydrate form. Our isolation protocol simplified the overall unit operations by evading aqueous workup and distillation, which was required in the isolation of the sodium sulfinate counterpart. Furthermore, this new process reduced the process mass intensity (PMI) by 3-fold and produced up to 2.32 kg of a magnesium aryl sulfinate tetrahydrate salt en route to an ERAP1 (endoplasmic reticulum aminopeptidase 1) drug candidate.

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亚硫酸盐水化制备四水合镁的流线型分离

通过水合作用和溶解度的相互作用，使四水亚硫酸亚芳基镁盐的流线型分离成为可能。我们发现，在芳基溴化镁和1,4-重氮杂环[2.2.2]辛烷二氧化硫（DABSO）的反应结束时加入少量的水，可以沉淀出稳定的四水合物形式的芳基亚硫酸镁盐。我们的分离方案简化了整个单元操作，避免了分离亚硫酸钠所需的水处理和蒸馏。此外，该新工艺将工艺质量强度（PMI）降低了3倍，并在生产ERAP1（内质网氨基肽酶1）候选药物的过程中生产了高达2.32 kg的亚硫酸芳基镁四水合物盐。

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.