| 第 49 卷第 2 期 |  | Vol. 49 No. 2 | | 2019 年 4 月 | Apr 2019 |
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所屬欄目：醫藥及中間體
1-（5-氟戊基）-1H-吲哚-3-羧酸的公斤級合成工藝研究 |
| 宋窈瑤，李 杰，王新龍，梁 淇
（成都艾必克醫院科技有限公司，四川 成都 610000） |
| 摘 要：對1-（5-氟戊基）-1H-吲哚-3-羧酸的合成工藝進(jìn)行了優(yōu)化，以?xún)r(jià)廉易得的吲哚為起始原料，經(jīng)傅-克�；�、鹵仿反應、N-烷基化、水解4步反應制備了目標化合物1-（5-氟戊基）-1H-吲哚-3-羧酸，總收率43.6%，產(chǎn)物純度>99%，其結構經(jīng)1H NMR和13C NMR表征確證。對吲哚N-烷基化的工藝進(jìn)行了優(yōu)化，采用溫和易得的混合堿［n（LiOH·H2O）∶n（KOH）=5∶1］一步引入5-氟戊基側鏈，革除了NaH的使用，工藝過(guò)程操作簡(jiǎn)便，反應條件溫和，溶劑低毒且可回收套用，大大提升了反應的安全性，適用于工業(yè)化生產(chǎn)同時(shí)為其他吲哚N-烷基化反應的工業(yè)化生產(chǎn)提供了新的思路。 |
| 關(guān)鍵詞：1-（5-氟戊基）-1H-吲哚-3-羧酸；N-烷基化；混合堿 |
| 中圖分類(lèi)號：TQ463 文獻標識碼：A 文章編號：1009-9212（2019）02-0026-04 |
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| A Kilo-scale Process for the Preparation of 1-(5-Fluoropentyl)-1H-indole-3-carboxylic Acid |
| SONG Yao-yao, LI Jie, WANG Xin-long, LIANG Qi
(Chengdu Aibike Pharmaceutical Co., Chengdu 610000, China) |
| Abstract：1-(5-Fluoropentyl)-1H-indole-3-carboxylic acid was synthesized from cheap and easy-afforded indole through a four- steps reactions including Friedel-Crafts acylation, haloform reaction, N-alkylation and hydrolyzation with an overall yield of 43.6% and a purity of 99%. The product structure was confirmed by 1H NMR and 13C NMR. The N-acylation process of indole emphatically screened. A facile and easy-afforded mixed base of n（LiOH·H2O）∶n（KOH）=5∶1 was chose to induced 5-fluoropentyl side chain in one step. The process avoided utilization of NaH and improved the reaction security. Meanwhile, the process provided a new idea for industrial synthesis of other indole N- alkylation products. This improved synthetic route had the advantages of easy preparation and mild reaction conditions. The reaction solvents was of low toxic and reutilization and suitable for industrial production. |
| Key words：1-(5-fluoropentyl)- 1H-indole-3-carboxylic acid; N-alkylation; mixed base |
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作者簡(jiǎn)介：宋窈瑤（1989-），女，四川眉山人，工程師，碩士研究生，研究方向：藥物合成工藝。
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收稿日期：2019-04-10
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