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

作者：Cantillo David; Ingle**y Phillip A; Boyd Alistair; Kappe C Oliver^*

来源：Journal of Flow Chemistry, 2017, 7(2): 29-32.

DOI：10.1556/1846.2017.00006

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

A safe and scalable procedure for the synthesis of 2-oxopropanethioamide, an intermediate in the synthesis of a potent beta-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.

• 出版日期2017-6