| 第 52 卷第 6 期 |  | Vol. 52 No. 6 | | 2022 年 12 月 | Dec 2022 |
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所属栏目：医药及中间体
布南色林关键中间体的合成工艺改进 |
| 段世辉，曾乐乐，潘玉平，彭泽根
（湖南省湘中制药有限公司，湖南 邵阳 442001） |
| 摘 要：在氢化钠催化下，对氟苯甲腈与乙腈反应得3-（4-氟苯基）-3-氧代丙腈，再经硫酸锆催化下水解制得3-（4-氟苯基）-3-氧代丙酰胺，最后在N，N-二甲基吡啶催化下与环辛酮环合得到布南色林关键中间体4-（4-氟苯基）-5，6，7，8，9，10-六氢环辛烷并［b］吡啶-2（1H）-酮，总收率90.0%。该方法条件温和，收率达95.0%，产物纯度99.4%以上（HPLC），满足绿色环保产业化要求。 |
| 关键词：布南色林；关键中间体；工艺改进 |
| 中图分类号：TQ463 文献标识码：A 文章编号：1009-9212（2022）06-0034-04 |
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| Synthesis of Key Intermediate of Bunanselin |
| DUAN Shi-hui, ZENG Le-le, PAN Yu-ping, PENG Ze-gen
(Hunan Xiangzhong Pharmaceutical Co., Ltd., Shaoyang 442001, China) |
| Abstract：The key intermediate of Bunanserin 3-(4-fluorophenyl)-3-oxopropylonitrile was prepared from the reaction of p-fluorobenzonitrile with acetonitrile in the presence of sodium hydride, and then was hydrolyzed to obtain 3-(4-fluorophenyl)-3-oxopropynamide in the presence of zirconium sulfate. Finally, 4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocyclooctano[b]pyridine-2(1H)-one was obtained by cyclization with cyclohexanone in the presence of N,N-dimethylpyridine with an overall yield of 90.0%. This method has advantages including no harsh conditions, high yield, and purity (above 99.4% HPLC), and meets the requirements of green environmental protection industrialization. |
| Key words：Blonanserin; key intermediate; process improvement |
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基金项目：湖南省创新创业技术投资项目（2017GK5045）。
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作者简介：段世辉（1968—），男，湖南武冈人，工程师，研究方向：药物和精细化工品研究和应用（E-mail：duanshihui2004@126.com）。
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收稿日期：2022-11-01
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