阿折地平的合成

Synthesis of Azelnidipine

二苯甲胺和环氧氯丙烷经亲核取代、闭环、酯化、加成等制得(N-羟基脒基)乙酸-1-二苯甲基氮杂环丁烷-3-基酯(4),4再经Pd/C催化氢化得到脒基乙酸-1-二苯甲基氮杂环丁烷-3-基酯乙酸盐(5)。另由间硝基苯甲醛和乙酰乙酸异丙酯在乙酸哌啶催化下反应制得2-(3-硝基亚苄基)乙酰乙酸异丙酯(6)。5和6经Michael加成、环合反应制得阿折地平,总收率约40%(以二苯甲胺计)。

Azelnidipine was synthesized from diphenyl amine and epichlorohydrin by nucleophilic substitution, cyclization, esterification, addition and reduction with Pd/C to give 1-benzhydrylazetidin-3-yl amidinoacetate acetic acid salt （5）, which was subjected to Michael addition with 2-（3-nitrobenzylidene）acetyl isopropyl acetate （6） and then cvclization with an overall yield of about 40%.