1．4──二氢吡啶类钙拮抗剂的合成法研究Ⅲ非洛地平的合成

STUDY ON SYNTHESIS FOR THE CALCIUM ANTAGONTST ⅢSYNTHESIS OF FELODIPINE

在无水氯化锌的存在下，２，３－二氯苯甲醛与乙酰乙酸甲酯经Ｋｎｏｅｖｅｎａｇｅｌ－Ｄｏｅｂｎｅｒ缩合反应，制成２，３－二氯亚苄基乙酰乙酸甲酯（２），继而与３－氨基丁烯酸甲酯在阳离子交换树脂Ｄ６１的催化下进行环合Ｍｉｃｈａｅｌ加成反应，得非洛地平（１），以２，３－二氯苯甲醛计算，总收率７６．５％。探计了无水氯化锌的用量，反应温度对２收率的影响，还考察了不同阳离子交换成树脂对１的收率和质量的影响。

Dichlordenzaldehyde treated with methyl acetoacetate via Knoevenagel -Doebner con-densation in the presena of anhydrous ZnCl_2 to give methyl 2,3-dichlorobenzylidene acetoacetate(2),which reacted with ethyl 3-aminocrotonate in the presence of cation exchange resin D 61 bycyclising Michael addition tO afford felodipine. The total yield was 76.5% based on 2,3-dicniorobenzaldehyde, The effect of quantity of anhydrous ZnCl_2 and reaction tempcrature on yieldof 2 was investigated. The influene of different cation exchange resins on yield and quality of 1 wasalso observed.The mild reations,convenient work-up and higer purity of the productwere the advantages of this process.