Isolation, characterization, and synthesis of some process-origin impurities of Atovaquone, a renowned anti-malarial drug
DOI:
https://doi.org/10.12723/mjs.70.6Keywords:
Atovaquone, 2,3-Dichloro-1,4-naphthoquinone, Impurities, Isolation, Characterization, SynthesisAbstract
To improve the yield of Atovaquone, we explored the chemical consequences occurring during its step-wise synthesis (process chemistry). Hence, the entire focus of this initiative was aimed towards the isolation of a few major process origin byproducts that were formed during the two-step reaction process. The synthesis of Atovaquone was done by the use of commercially viable key starting material trans-4-(4-chlorophenyl) cyclohexanecarboxylic acid for the decarboxylative coupling reaction with another key reactant 2,3-dichloro-1,4-naphthoquinone to obtain the intermediate. The isolated intermediate was hydrolyzed to obtain Atovaquone. From the mother liquors (MLRs) of each stage, we were able to isolate a few major process origin impurities and characterize them with the assistance of spectral data. Additionally, we even synthesized some of the impurities and compared them with the ones that were isolated from the MLRs. In this work, we report the experimental aspects and results related to six process-origin impurities of Atovaquone.
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