| 第 52 卷第 6 期 |  | Vol. 52 No. 6 | | 2022 年 12 月 | Dec 2022 |
|
所屬欄目：醫藥及中間體
布南色林關(guān)鍵中間體的合成工藝改進(jìn) |
| 段世輝，曾樂(lè )樂(lè )，潘玉平，彭澤根
（湖南省湘中制藥有限公司，湖南 邵陽(yáng) 442001） |
| 摘 要：在氫化鈉催化下，對氟苯甲腈與乙腈反應得3-（4-氟苯基）-3-氧代丙腈，再經(jīng)硫酸鋯催化下水解制得3-（4-氟苯基）-3-氧代丙酰胺，最后在N，N-二甲基吡啶催化下與環(huán)辛酮環(huán)合得到布南色林關(guān)鍵中間體4-（4-氟苯基）-5，6，7，8，9，10-六氫環(huán)辛烷并［b］吡啶-2（1H）-酮，總收率90.0%。該方法條件溫和，收率達95.0%，產(chǎn)物純度99.4%以上（HPLC），滿(mǎn)足綠色環(huán)保產(chǎn)業(yè)化要求。 |
| 關(guān)鍵詞：布南色林；關(guān)鍵中間體；工藝改進(jìn) |
| 中圖分類(lèi)號：TQ463 文獻標識碼：A 文章編號：1009-9212（2022）06-0034-04 |
|
| 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 |
|
基金項目：湖南省創(chuàng )新創(chuàng )業(yè)技術(shù)投資項目（2017GK5045）。
|
作者簡(jiǎn)介：段世輝（1968—），男，湖南武岡人，工程師，研究方向：藥物和精細化工品研究和應用（E-mail：duanshihui2004@126.com）。
|
收稿日期：2022-11-01
|
|