Heng Chen*, Aaron C. Spahr, Alan J. Shaffer, Rebecca J. W. Beck and Todd W. Koretke,
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Streamlined Isolation of Magnesium Aryl Sulfinate Enabled by the Hydration of Sulfinate Salt to Magnesium Tetrahydrate
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.
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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