Synthesis of Dolutegravir Exploiting Continuous Flow Chemistry

An efficient continuous flow process for the synthesis of dolutegravir, an active pharmaceutical ingredient (API) for HIV treatment, was investigated. The synthetic procedure starts from a readily available benzyl-protected pyran via six chemical transformations using continuous flow reactors. The significant advantage of this flow process includes the reduction of the overall reaction time from 34.5 h in batch to 14.5 min. The overall yield of each reaction step improved dramatically upon flow optimization. Another key feature of this synthesis is telescoping multiple steps.