超声波辐射技术合成氯雷他定

Ultrasound Irradiation Supported Synthesis of Loratadine

摘要:

以氨气和丙烯酸甲酯为起始原料，经Michael加成、Dieckmann环合、脱羧、乙氧羰基化和McMurry反应合成了4-(8-氯-5,6-二氢-11H-苯并[5,6]环庚并[1, 2-b]吡啶-11-亚基)-1-哌啶羧酸乙酯（氯雷他定）。McMurry反应以超声辐射为反应条件，并对McMurry反应涉及的工艺参数进行了优化，采用核磁共振波谱对产物进行了表征。结果表明：n（8-氯-10,11-二氢-4-氮杂-5H-二苯并[a,d]-5-环庚酮）：n（N-乙氧羰基-4-哌啶酮）：n（TiCl4）：n（Zn）=1: 1.2: 4: 6.8，在频率为25kHz的超声波和67℃（回流温度）下反应30min，收率为88.5%，目标产物（氯雷他定）的总收率为57.8%。

Abstract:

4-(8-Chlor-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridine-11-ylidene)-1-piperi-dine carboxylic acid ethyl ester (Loratadine) was prepared from ammonia and methyl acrylate through Michael addition, Dieckmann cyclization, decarboxylation, ethoxy carbonylation and McMurry reaction. The conditon of McMurry reaction was conducted under ultrasound irradiation, and technological parameters involved in McMurry reation were optimized. Structures of the title compound and the intermediates were confirmed by 1HNMR. The results show that n(8-chloro-10,11-dihydro-4-aza-5H-dibenzo[a,d]cyclohepten-5-one):n(N-ethoxycarbonyl-4-piperidone):n(TiCl4):n(Zn)= 1:1.2:4:6.8 reacted under 25kHz and 67℃（under reflux）for 30min to give the intermediate in 88.5%, and the total yield of target compound（Loratadine） was 57.8%.