Development of a Safe Continuous Manufacturing Route to 2-(4-Isopropyl-1H-1,2,3-triazol-1-yl)acetic Acid

Starting from sodium azide, methyl-bromoacetate, and 3-methylbut-1-yne, a safe and efficient three-step continuous process was developed to obtain 2-(4-isopropyl-1H-1,2,3-triazol-1-yl)acetic acid. Isolation of hazardous intermediates was avoided, and by using FT-IR in-line monitoring of the azides involved, risks associated with these components were minimized. Furthermore, the use of FT-IR as a tool for optimization in real time facilitated the understanding of the kinetics of the reaction steps and resulted in a rapid optimization of parameters. The continuous method was used for multihundred grams manufacturing of the triazole which was used as a key building block in one of our drug development projects.