Research on Chemical Intermediates p. 2107 - 2113 (2013)
Update date:2022-08-10
Topics:
Lin, Yan
Huang, Peijun
Liu, Shuai
Sima, Lifeng
Chen, Ligong
Wang, Donghua
A convenient synthetic method has been developed for the synthesis of roflumilast from 4-difluoromethoxy-3-hydroxybenzaldehyde and bromomethyl cyclopropane via O-alkylation, oxidation and N-acylation. With sodium hydroxide as alkali in the last step, the total yield of roflumilast can be up to 68.3 % and the purity of the target product reached 99.2 %. It was obvious that sodium hydroxide showed more economic advantage for scale-up production than sodium hydride or potassium tert-butoxide.
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Doi:10.1002/jps.3030430312
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