High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine

Beilstein J Org Chem. 2018 Mar 8:14:583-592. doi: 10.3762/bjoc.14.45. eCollection 2018.


Numerous synthetic methods for the continuous preparation of fine chemicals and active pharmaceutical ingredients (API's) have been reported in recent years resulting in a dramatic improvement in process efficiencies. Herein we report a highly efficient continuous synthesis of the antimalarial drug hydroxychloroquine (HCQ). Key improvements in the new process include the elimination of protecting groups with an overall yield improvement of 52% over the current commercial process. The continuous process employs a combination of packed bed reactors with continuous stirred tank reactors for the direct conversion of the starting materials to the product. This high-yielding, multigram-scale continuous synthesis provides an opportunity to achieve increase global access to hydroxychloroquine for treatment of malaria.

Keywords: API manufacturing; antimalarial; flow chemistry; hydrogenation; hydroiodic acid; hydroxychloroquine.