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Hydrogen Sulfide Chemistry in Continuous Flow: Efficient Synthesis of 2-Oxopropanethioamide

Abstract

A safe and scalable procedure for the synthesis of 2-oxopropanethioamide, an intermediate in the synthesis of a potent β-secretase (BACE-1) inhibitor, from the reaction of acetyl cyanide with hydrogen sulfide gas under continuous-flow conditions has been developed. The toxic gas could be accurately dosed using a mass-flow controller or a peristaltic pump. The reaction proceeded smoothly at room temperature in the presence of a small amount of triethylamine as basic catalyst. After a residence time of 15 min, excellent yield (96%) and purity (>99%) were obtained for the target compound. The high reaction selectivity permitted a simple workup procedure consisting of evaporation of all volatiles.

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Correspondence to C. Oliver Kappe.

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Cantillo, D., Inglesby, P.A., Boyd, A. et al. Hydrogen Sulfide Chemistry in Continuous Flow: Efficient Synthesis of 2-Oxopropanethioamide. J Flow Chem 7, 29–32 (2017). https://doi.org/10.1556/1846.2017.00006

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  • DOI: https://doi.org/10.1556/1846.2017.00006

Keyword

  • Microreactors
  • hydrogen sulfide
  • gas-liquid processing
  • continuous processing
  • active pharmaceutical ingredients