The assembly of integrated continuous flow platform for on-demand rosiglitazone and pioglitazone synthesis

Abstract

Manufacturing thiazolidinediones in a batch process is often carried out at different locations, where each successive batch collects a certain amount of intermediate followed by its transportation to another location. Thiazolidinediones containing APIs are unstable at ambient temperature. In this regard, manufacturing sites need huge storage capacity with lower temperature (2–8 °C), which eventually increases the production cost. Another problem with the individual batch mode is regarding the strict regulatory control to monitor successive batches. If any batch product parameter doesn't match with the regulatory approved specification, then the entire batch must be discarded or reprocessed, which results in high manufacturing price and renders it unaffordable. Herein, we have developed an integrated continuous flow nucleophilic substitution, Knoevenagel condensation, and hydrogenation reaction (NKH) platform for the on-demand production of thiazolidinediones in 32.5 min residence time with an overall improved yield.