布南色林中间体合成工艺的改进Improved Synthesis of Intermediate of Blonanserin
汪岩峰,余卫麟,胡克余,马俊
WANG Yanfeng,YU Weilin,HU Keyu,MA Jun
摘要(Abstract)：
目的研究与改进布南色林中间体的合成工艺。4-(4-氟苯基)-5,6,7,8,9,10-六氢环辛烷并[b]吡啶-2(1H)-酮(化合物3)为合成5-羟色胺类受体拮抗剂布南色林的关键中间体,现有方法存在产物复杂、分离难、收率低、搅拌困难且易爆沸的问题。故需优化化合物3的合成工艺。方法以浓硫酸代替多聚磷酸合成3-(4-氟苯基)-3氧代丙酰胺及一水对甲苯磺酸先脱水再进行共沸脱水缩合制备化合物3。结果本方法解决了搅拌困难的问题并解除了爆沸冲料的缺陷。产物通过EA、MS、1H-NMR确定了结构。化合物3的纯度不小于99.5%,总收率从53.4%提高到64.1%。结论该方法简便可靠,重复性好,所得化合物3适用于布南色林原料药的起始原料的合成。
OBJECTIVE Study and improvement on the synthetic process of intermediate of blonanserin.4-( 4-fluorophenyl)-5,6,7,8,9,10-hexahydro-1H-cycloocta[b]pyridin-2-one is the intermediate of blonanserin which is the 5-serotonin receptor antagonist.There are the disadvantages of complex mixture so as to difficult to purify and low yield or difficult to agitate,easy to bump in the previous methods. METHODS Compound 3 was synthesized by 3-( 4-fluorophenyl)-3 oxygen generation acrylic amide and p-toluene sulfonic acid monohydrate dehydration and azeotropic dehydration condensation. RESULTS The above mentioned disadvantages were overcome.The structures of intermediates and product were identified by EA,MS and1H-NMR. The purity of compound 3 was not than less 99.5% and the total yields was up to 64.1% as the yield of the previous method was 53.4%. CONCLUSION The process is easy to operate especially has good reproducibility so as to it is suitable to used as the starting material of blonanserin manufacturing.
关键词(KeyWords)：
布南色林;水解;缩合;合成
blonanserin;hydrolysis;condensation;synthesis
基金项目(Foundation): 广东省科技计划项目(2012A080800010)
作者(Author):
汪岩峰,余卫麟,胡克余,马俊
WANG Yanfeng,YU Weilin,HU Keyu,MA Jun
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