Isolation, synthesis and structure confirmation of the impurity in crude roflumilast product.

An impurity was isolated from crude synthesized roflumilast and characterized by H NMR, C NMR, and HR-MS, which confirmed the structure as N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-3-hydroxybenzamide. To further verify the structure, this compound was synthesized from 4-difluoromethoxy-3-hydroxybenzaldehyde. Comparison of the H NMR, C NMR, HR-MS, and the HPLC spectrum of the impurity and the authentic sample indicated that this impurity was N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-3-hydroxybenzamide. This demonstrated the significance of monitoring the reaction process of roflumilast. [ABSTRACT FROM AUTHOR]