| 第 49 卷第 6 期 |  | Vol. 49 No. 6 | | 2019 年 12 月 | Dec 2019 |
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所屬欄目：醫藥及中間體
4-（4-乙基苯基）甲基-1，3-二氫異苯并呋喃的合成工藝研究 |
| 李 娟1，李匡元2，張軍偉1
（1. 西安萬(wàn)隆制藥股份有限公司，陜西 西安 710119；2. 陜西萬(wàn)盛健康產(chǎn)業(yè)有限公司，陜西 西安 710000） |
| 摘 要：以1-溴甲基-4-乙基苯為起始原料，經(jīng)硼酸化、Suzuki偶聯(lián)等反應制備了4-（4-乙基苯基）甲基- 1，3-二氫異苯并呋喃，其結構經(jīng)1H NMR和MS確證。對合成過(guò)程關(guān)鍵工藝參數進(jìn)行優(yōu)化，優(yōu)化工藝路線(xiàn)為，硼酸化反應：n（1-溴甲基-4-乙基苯）∶n（硼酸三丁酯）=1.0∶1.3、正丁基鋰滴加速率為600 mL·h-1、n（乙酸乙酯）∶n（環(huán)己烷）=1∶2；Suzuki偶聯(lián)反應：Pd（PPh3）4質(zhì)量分數為5.0%、反應溫度為65~75℃。反應總收率62.6%，純度99.5%，滿(mǎn)足高品質(zhì)醫藥中間體的要求。該合成工藝穩定、操作簡(jiǎn)便，具有較好的應用價(jià)值。 |
| 關(guān)鍵詞：二芳基甲烷；異苯并呋喃；Suzuki偶聯(lián)；4-（4-乙基苯基）甲基- 1，3-二氫異苯并呋喃 |
| 中圖分類(lèi)號：O622.6 文獻標識碼：A 文章編號：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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作者簡(jiǎn)介：李 娟（1978-），女，陜西長(cháng)安人，執業(yè)藥師，主要從事醫藥產(chǎn)品研發(fā)、藥品質(zhì)量研究及質(zhì)量管理工作。
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收稿日期：2019-11-05
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