布南色林的合成

Synthesis of Blonanserin

布南色林是一种新型非典型抗精神病药物。本研究是在中试规模研究其合成工艺。具体步骤如下:由氟苯甲酸甲酯与乙腈在氢化钠碱性条件下缩合得对氟苯甲酰乙腈,再与75%的多聚磷酸和环辛酮环合,一步得到4-(4-氟苯基)-5,6,7,8,9,10-六氢-环辛烷并[b]吡啶-2(1H)-酮,与三溴氧磷发生溴化反应生成2-溴-4-(4-氟苯基)-5,6,7,8,9,10-六氢-环辛烷并[b]吡啶,最后与N-乙基哌嗪在碳酸钾、碘化钾催化下进行亲核取代反应,得到布南色林,总收率约52.2%。

Blonanserin is a kind of new atypical antipsychotics. A pilot scale research in the synthesis process was carried out. 4 - （4-fluorophenyl） -5,6,7,8,9,10-hexahydroeyeloocta [ b ] pyridin-2 （1H） -one was synthesized from methyl 4-fluorobenzoate and acetonitrile, in the presence of sodium hydride to give 4-fluorobenzoylcatonitrile, followed by the cyclization in 75 % polyphosphoric acid with cyclooctanone. By using phosphorusoxidebromide, 2 - bromo- 4 - （ 4 - fluorophenyl）-5,6,7,8,9,10-hexahydroeyeloocta[ b ] pyridine was given by bromization and had condensation with N- ethyl piperazine in the presence of potassium carbonate and potassium iodide to give blonanserin with an overall yield of 52.2%.