CN103319370A - Preparation method of (7-methoxy-1-naphthyl)acetonitrile - Google Patents
Preparation method of (7-methoxy-1-naphthyl)acetonitrile Download PDFInfo
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- CN103319370A CN103319370A CN2012100753153A CN201210075315A CN103319370A CN 103319370 A CN103319370 A CN 103319370A CN 2012100753153 A CN2012100753153 A CN 2012100753153A CN 201210075315 A CN201210075315 A CN 201210075315A CN 103319370 A CN103319370 A CN 103319370A
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Abstract
The invention relates to a preparation method of (7-methoxy-1-naphthyl)acetonitrile, a compound represented by formula (I). (7-methoxy-3,4-naphthyl)acetonitrile, a compound represented by formula (II), is reacted with hydrogenation catalysts in the presence of 4A molecular sieves; and (7-methoxy-1-naphthyl)acetonitrile is obtained after separation. (7-methoxy-1-naphthyl)acetonitrile is an important intermediate for preparing agomelatine.
Description
Technical field
The invention belongs to technical field of organic synthesis, the method for particularly a kind of preparation (7-methoxyl group-1-naphthyl) acetonitrile can be used as the intermediate for preparing Agomelatine.
Background technology
Agomelatine is mainly used in treating melatonin energy systemic disease, its character makes it possess activity in central nervous system, especially at severe depression, seasonal affective disorder, somnopathy, cardiovascular disorder, digestive system, the insomnia that jet lag causes and fatigue have activity in the treatment of appetite disorder and obesity.Therefore developing Agomelatine has favorable economic benefit and social benefit.
Formula (I) compound is the important intermediate of synthetic Agomelatine.Reported the ordinary method of synthetic compound (I) among the patent CN1680284, this method generates intermediate formula (II) compound by 7-methoxyl group-1-Tetralone an intermediate of Sertraline and cyanoacetic acid reaction, intermediate (II) is under the effect of hydrogenation catalyst palladium charcoal, be that dehydrogenating agent carries out dehydrogenation with the allyl methacrylate(AMA), obtain compound shown in the formula (I).This method yield is lower, and allyl methacrylate(AMA) toxicity is bigger, and environment is polluted.
Reported the synthetic of (7-methoxyl group-1-naphthyl) acetonitrile among the US5194614, wherein relate to six reactions steps and obtain target compound, but the yield of its first step has been lower, and poor reproducibility, do not meet industrial production requirement.
Based on the pharmacy value of Agomelatine and good market outlook, the effective ways of seeking the synthesis type that a kind of yield is good and controllability is strong (I) are imperative.
Summary of the invention
The technical problem that the present invention solves is to overcome the deficiencies in the prior art, and the preparation method of a kind of (7-methoxyl group-1-naphthyl) acetonitrile is provided.
The objective of the invention is to be achieved through the following technical solutions, may further comprise the steps:
1) 7-methoxyl group-1-Tetralone an intermediate of Sertraline and cyanoacetic acid reaction production (II) compound;
2) in reaction vessel, add dimethyl sulfoxide (DMSO), formula (II) compound, palladium charcoal and molecular sieve, backflow stirring reaction 3-5 hour;
3) with reacting liquid filtering, gained filtrate extracts through toluene, and concentrate drying had both got (7-methoxyl group-1-naphthyl) acetonitrile.
The present invention uses molecular sieve and palladium charcoal as Preparation of Catalyst (7-methoxyl group-1-naphthyl) acetonitrile on the prior art basis, compared with prior art, has improved speed of response and yield greatly, and target product yield can reach 93%.Preparation method's production cost of the present invention is low, is suitable for suitability for industrialized production, also helps the reduction of derived product Agomelatine cost simultaneously.
Embodiment
Embodiment 1:
In the reaction flask of drying, add dimethyl sulfoxide (DMSO) 400mL and (7-methoxyl group-3,4-naphthyl) acetonitrile 200g (1.0mol), the stirring at room dissolving; In above-mentioned solution, add 4A molecular sieve 20g and palladium charcoal (5%) 10g, heating reflux reaction 4.5 hours, filtering reacting liquid, filtrate extracts with toluene, and the organic phase concentrate drying had both got (7-methoxyl group-1-naphthyl) acetonitrile 190g, yield 95%.
The above embodiment only is that preferred implementation of the present invention is described; be not that scope of the present invention is limited; design under the prerequisite of spirit not breaking away from the present invention; various distortion and improvement that those of ordinary skills make technical scheme of the present invention all should fall in the definite protection domain of claims of the present invention.
Claims (5)
1. method for preparing (7-methoxyl group-1-naphthyl) acetonitrile, it is characterized in that formula (II) compound is in the presence of molecular sieve, with the hydrogenation catalyst reaction, after desolventizing, filtration and steaming obtain formula (I) compound, come out with isolated in solid form behind formula (I) the compound recrystallization:
2. the method for preparation formula (I) compound according to claim 1 is characterized in that described molecular sieve is the 4A molecular sieve.
3. the method for preparation formula (I) compound according to claim 1 is characterized in that described hydrogenation catalyst is 5% palladium charcoal.
4. the method for preparation formula (I) compound according to claim 1 is characterized in that described catalyst levels is 5% of substrate weight with respect to the weight meter of substrate.
5. the method for preparation formula (I) compound according to claim 1 is characterized in that described being reflected in the dimethyl sulfoxide (DMSO) carried out.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210075315.3A CN103319370B (en) | 2012-03-21 | 2012-03-21 | A kind of preparation method of (7-methoxy-1-naphthyl) acetonitrile |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201210075315.3A CN103319370B (en) | 2012-03-21 | 2012-03-21 | A kind of preparation method of (7-methoxy-1-naphthyl) acetonitrile |
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| CN103319370A true CN103319370A (en) | 2013-09-25 |
| CN103319370B CN103319370B (en) | 2016-08-03 |
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| CN201210075315.3A Active CN103319370B (en) | 2012-03-21 | 2012-03-21 | A kind of preparation method of (7-methoxy-1-naphthyl) acetonitrile |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1038805A (en) * | 1988-06-24 | 1990-01-17 | 阿莫科公司 | The preparation method of dimethyltetralin |
| CN1490293A (en) * | 2002-10-15 | 2004-04-21 | 徐州瑞赛科技实业有限公司 | Preparation of o-phenyl phenol from cyclohexanone by condense dehydrogenation |
| WO2005077887A1 (en) * | 2004-02-13 | 2005-08-25 | Les Laboratoires Servier | Novel method of synthesis and novel crystalline form of agomelatine and pharmaceutical compositions containing said form |
| CN1680296A (en) * | 2004-02-13 | 2005-10-12 | 瑟维尔实验室 | New process for the synthesis of (7-methoxy-1-naphthyl)acetonitrile and application in the synthesis of agomelatine |
| CN101161638A (en) * | 2006-10-13 | 2008-04-16 | 北京德众万全药物技术开发有限公司 | Method for preparing novel agomelatine key intermediates |
-
2012
- 2012-03-21 CN CN201210075315.3A patent/CN103319370B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1038805A (en) * | 1988-06-24 | 1990-01-17 | 阿莫科公司 | The preparation method of dimethyltetralin |
| CN1490293A (en) * | 2002-10-15 | 2004-04-21 | 徐州瑞赛科技实业有限公司 | Preparation of o-phenyl phenol from cyclohexanone by condense dehydrogenation |
| WO2005077887A1 (en) * | 2004-02-13 | 2005-08-25 | Les Laboratoires Servier | Novel method of synthesis and novel crystalline form of agomelatine and pharmaceutical compositions containing said form |
| CN1680296A (en) * | 2004-02-13 | 2005-10-12 | 瑟维尔实验室 | New process for the synthesis of (7-methoxy-1-naphthyl)acetonitrile and application in the synthesis of agomelatine |
| CN101161638A (en) * | 2006-10-13 | 2008-04-16 | 北京德众万全药物技术开发有限公司 | Method for preparing novel agomelatine key intermediates |
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| CN103319370B (en) | 2016-08-03 |
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Address after: No.1166 Zhengyang Street, Zhaodong City, Suihua City, Heilongjiang Province Patentee after: HEILONGJIANG FUHE PHARMACEUTICAL GROUP Co.,Ltd. Address before: 151100 No. 34 Taiping Road, Suihua, Heilongjiang, Zhaodong Patentee before: HEILONGJIANG FUHE HUAXING PHARMACEUTICAL GROUP Co.,Ltd. |