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.