Scalable Continuous Flow Reduction for the Synthesis of Emtricitabine

Emtricitabine (FTC) is an important antiretroviral drug with a growing market, highlighting the need for local production with large-scale potential. With continuous flow synthesis increasingly explored across a wide range of APIs, applying this approach to FTC offers the potential for improved scalability and process efficiency. This study developed a continuous flow method for FTC, addressing feed stability and optimizing reaction conditions to enable stable, long-duration operation at scalable throughput. The optimized continuous flow process maintained consistent yields from 60 to 78% when scaling from 2 to 50 g of the starting material. Comparative evaluation with traditional batch synthesis showed that the flow approach achieves high product quality with the purity of >98%, exceptional productivity measuring as a space-time-yield (STY) of 5.25 kg FTC (L·day)–1, while a 50% reduction in environmental impact. Moreover, the ability of the same continuous flow setup to perform the identical ester-reduction step in a structurally analogous API, lamivudine (3TC), further demonstrates its versatility and broader applicability to similar reaction systems.