罗氟司特的合成

Synthesis of Roflumilast

3,4-二羟基苯甲醛与二氟一氯甲烷醚化得到3-羟基-4-二氟甲氧基苯甲醛,与氯甲基环丙烷醚化得到3-环丙基甲氧基-4-二氟甲氧基苯甲醛,再经氧化、氯代后与4-氨基-3,5-二氯吡啶反应,制得慢性阻塞性肺病治疗药罗氟司特,总收率约23%。

Roflumilast, an anti-chronic obstructive pulmonary disease （COPD） drug, was synthesized from 3,4- dihydroxybenzaldehyde via etherification with chlorodifluoromethane to give 3-hydroxy-4-difluoromethoxybenzaldehyde, which was subjected to etherification with chloromethylcyclopropane to give 3-eyclopropylmethoxy-4-difluoro- methoxybenzaldehyde, followed by oxidation, chlorination and then reaction with 4-amino-3,5-dichloropyridine with an overall yield of about 23 %.