Synthesis study of acetal impurities in warfarin sodium
Objective:To synthesize the impurities WF-Z1-WF-Z6 produced in the production process of warfarin sodium.Methods:Using 2′-hydroxyacetophenone(SM-1)as a starting material,4-hydroxy-chromen-2-one(WF-1)was synthesized by condensation reaction with dimethyl carbonate(SM-2).Subsequently,Michael addition reaction with 4-phenyl-3-buten-2-one(SM-3)was carried out to obtain 3-(α-acetoneylbenzyl)-4-hydroxycoumarin(WF),and finally the corresponding target impurities WF-Z1-WF-Z6 were synthesized by reaction with methanol,ethanol or isopropanol under acidic conditions.Results:The chemical structure of these impurities were identified by LCMS,1H NMR,13C NMR.Conclusion:The synthesized impurities can be used as a reference material for the quality control of warfarin sodium and moreover,the starting materials used in this synthetic route are cheap and easy to obtain and it is expected to be used in industrial production.
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