| 第 49 卷第 6 期 |  | Vol. 49 No. 6 | | 2019 年 12 月 | Dec 2019 |
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所属栏目：医药及中间体
4-（4-乙基苯基）甲基-1，3-二氢异苯并呋喃的合成工艺研究 |
| 李 娟1，李匡元2，张军伟1
（1. 西安万隆制药股份有限公司，陕西 西安 710119；2. 陕西万盛健康产业有限公司，陕西 西安 710000） |
| 摘 要：以1-溴甲基-4-乙基苯为起始原料，经硼酸化、Suzuki偶联等反应制备了4-（4-乙基苯基）甲基- 1，3-二氢异苯并呋喃，其结构经1H NMR和MS确证。对合成过程关键工艺参数进行优化，优化工艺路线为，硼酸化反应：n（1-溴甲基-4-乙基苯）∶n（硼酸三丁酯）=1.0∶1.3、正丁基锂滴加速率为600 mL·h-1、n（乙酸乙酯）∶n（环己烷）=1∶2；Suzuki偶联反应：Pd（PPh3）4质量分数为5.0%、反应温度为65~75℃。反应总收率62.6%，纯度99.5%，满足高品质医药中间体的要求。该合成工艺稳定、操作简便，具有较好的应用价值。 |
| 关键词：二芳基甲烷；异苯并呋喃；Suzuki偶联；4-（4-乙基苯基）甲基- 1，3-二氢异苯并呋喃 |
| 中图分类号：O622.6 文献标识码：A 文章编号：1009-9212（2019）06-0041-05 |
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| Synthetic Process of 4-(4-Ethylphenyl)methyl-1,3-dihydro-isobenzofuran |
| LI Juan1, LI Kuang-yuan2, ZHANG Jun-wei1
(1. Xi'an Wanlong Pharmaceutical Co., Ltd., Xi'an 710119, China; 2. Shaanxi Wansheng Health Industry Co.,Ltd., Shaanxi, Xi'an 710000, China) |
| Abstract：4-(4-Ethylphenyl)methyl-1,3-dihydro-isobenzofuran was synthesized in a two-step reaction including boric acidification and Suzuki coupling reaction using1-(bromomethyl)-4-ethylbenzene as the starting material. The structure of this target product was confirmed by 1H NMR and MS. The main factors influencing the reaction were investigated by single factor experiments. The experimental results showed that in the boric acidification reaction, the molar ratio of 1-(bromomethyl)-4-ethylbenzene to tri-n-butyl borate was of 1.0∶1.3, the crystallization solvent molar ratio of ethyl acetate to cyclohexane was of 1∶2; in the Suzuki coupling reaction, the mass fraction of Pd(PPh3)4 is of 5.0%, the reaction temperature is of 65~75℃. The overall yield of 4-(4-ethylphenyl)methyl-1,3-dihydro-isobenzofuran was up to 62.6% with a purity of 99.5%, and this purity meet the demands of the higher quality for pharmaceutical intermediate. This synthetic process had the advantages including reasonable and feasible process, easy preparation and mild reaction conditions. It was of refereeing significance to the industrial production of 4-(4-ethylphenyl)methyl-1,3-dihydro-isobenzofuran and its downstream research of active pharmaceutical ingredients. |
| Key words：diarylmethane; isobenzofuran; Suzuki coupling; 4-(4-ethylphenyl)methyl-1,3-dihydro-isobenzofuran |
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作者简介：李 娟（1978-），女，陕西长安人，执业药师，主要从事医药产品研发、药品质量研究及质量管理工作。
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收稿日期：2019-11-05
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