In recent decades, flow chemistry has emerged as a vital tool for the manufacture of key intermediate for active pharmaceutical ingredient (API) and molecules of therapeutic interest. Herein, we report a high-yielding, safe and efficient formation of aryl turbo Grignard intermediate and its selective addition to highly enolizable 1,3-dichloroacetone, resulting in the formation of key pharmaceutical intermediate for fluconazole.<br/>Flow chemistry also provide the advantages of providing access to alternate reaction pathways and/or high energy intermediates, which are inaccessible in batch conditions. An excellent example is an efficient continuous synthesis of the antimalarial drug hydroxychloroquine (HCQ). Key improvements in our new process includes elimination of protecting groups with an overall yield improvement of 52% over current commercial process.

Application of continuous and semi-continuous flow methods in synthesis of active pharmaceutical intermediates in fluconazole and hydroxychloroquine

ACS Spring 2022

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