Synthesis of Dolutegravir Exploiting Continuous Flow Chemistry

[Image: see text] 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.