1369817-76-4Relevant articles and documents
Synthesis of an impurity in crude roflumilast
Zhang, Hankang,Lin, Yan,Li, Yan,Dong, Kai,Chen, Ligong,Wang, Donghua
, p. 507 - 509 (2014/11/08)
A simple synthetic method has been developed for the synthesis of 3,4-bis(cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl) benzamide (an impurity in crude roflumilast) from 3,4-dihydroxybenzaldehyde via alkylation, oxidation, chlorination and acylation reactions. Acetonitrile was used as the solvent in all the three steps for convenient recovery. The oxidation of 3,4-bis(cyclopropylmethoxy)benzaldehyde (purity, 86.2%) by sodium chlorite afforded the corresponding acid with purity of 99.2%. Finally, N-acylation of 3,5-dichloropyridin-4-amine yielded 3,4-bis(cyclopropylmethoxy)-N-(3,5- dichloropyridin-4-yl) benzamide. Without column chromatography, the overall yield of the target compound was about 70%.