Synthesis Of The Key Intermidiate For Antidepressant Drug Vilazodone

This dissertation mainly focuses on the novel synthetic technologies of tert-butyl 4-(2-(ethoxycarbonyl)benzofuran-5-yl)piperazine-1-carboxylte and tert-butyl 4-(2-carbamoylbenzofuran-5-yl)piperazine-1-carboxylate,which are important intermediates of antidepressant drug Vilazodone.The technologies succeed in reducing environmental pollution and reagent toxicity,because they avoid the highly toxic mechlorethamine hydrochloride by using the Ullmann coupling reaction to introduce a piperazine ring.The technologies also succeed in using cheap copper catalyst instead of expensive palladium catalyst.This dissertation consisted of three chapters:In the first chapter,we simply introduced Vilazodone,and presented the review of its total synthesis routes with different starting materials.In the second chapter,we mainly introduced the history of the development of the Ullmann coupling,described the reaction mechanism,and reviewed the Ullmann C-N coupling reaction on the basis of different ligands.In the third chapter,a novel technology was developed to synthesize tert-butyl 4-(2-(ethoxycarbonyl)benzofuran-5-yl)piperazine-1-carboxylate.The conditions of the selected route then were optimized.Finally,the yield of cyclization reaction was 60%,and the yield of Ullmann coupling reaction was 40.6%;Other technology also was developed to synthesize tert-butyl 4-(2-carbamoylbenzofuran-5-yl)piperazine-1-carboxylate.Through optimization,the yield of ammoniation reaction was 80.1%,and the yield of Ullmann coupling reaction was 48.2%.