西尼地平的合成

Synthesis of Cilnidipine

以双烯酮为原料 ,分别与乙二醇单甲醚和肉桂醇进行酯化反应制得乙酰乙酸 - 2 -甲氧基乙酯和乙酰乙酸肉桂酯 ,前者与间硝基苯甲醛缩合生成的 2 - (3-硝基亚苄基 )乙酰乙酸 2 -甲氧基乙酯和后者的氨化产物 3-氨基 - 2 -丁烯酸肉桂酯再进行 Hantzsch环化反应制得新型钙拮抗剂西尼地平。方法条件温和 ,反应总收率 6 8.3% (以肉桂酯计 )

Diketene reacted with 2-methoxyethanol and cinnamyl alcohol respectively gave 2-methoxyethyl acetoacetate and cinnamyl acetoacetate. 2-Methoxyethyl 2-(3-nitrobenzylidene) acetoacetate derived from the former reacted with cinnamyl 2-aminocrotonate derived from the latter under mild Hantzsch cyclization conditions produced new calcium antagonist cilnidipine. The total yield was 68.3% (based on cinnamyl alcohol).