CN103319370B - A kind of preparation method of (7-methoxy-1-naphthyl) acetonitrile - Google Patents
A kind of preparation method of (7-methoxy-1-naphthyl) acetonitrile Download PDFInfo
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- CN103319370B CN103319370B CN201210075315.3A CN201210075315A CN103319370B CN 103319370 B CN103319370 B CN 103319370B CN 201210075315 A CN201210075315 A CN 201210075315A CN 103319370 B CN103319370 B CN 103319370B
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Abstract
The present invention relates to the preparation method of formula (I) compound (7-methoxy-1-naphthyl) acetonitrile, in the presence of 4A molecular sieve, by formula (II) compound (7-methoxyl group-3,4-naphthyl) acetonitrile reacts with hydrogenation catalyst, is isolated to formula (I) compound (7-methoxy-1-naphthyl) acetonitrile.This compound is the important intermediate preparing agomelatine.
Description
Technical field
The invention belongs to technical field of organic synthesis, the method preparing (7-methoxy-1-naphthyl) acetonitrile particularly to one, can be as the intermediate preparing agomelatine.
Background technology
Agomelatine is mainly used in treating melatonin energy systemic disease, its character makes it possess activity central nervous system, especially at severe depression, seasonal affective disorder, sleep disorder, cardiovascular disease, digestive system disease, in insomnia that jet lag causes and the treatment of fatigue, appetite disorder and obesity active.Therefore exploitation agomelatine has preferable economic benefit and social benefit.
Formula (I) compound is the important intermediate of synthesis agomelatine.Patent CN1680284 reports the conventional method of synthesis compound (I), the method reacts generation intermediate formula (II) compound by 7-methoxyl group-ALPHA-tetralone and cyanoacetic acid, intermediate (II) is under hydrogenation catalyst palladium charcoal effect, carry out dehydrogenation with allyl methacrylate for dehydrogenating agent, obtain compound shown in formula (I).The method yield is relatively low, and allyl methacrylate toxicity is relatively big, to environment.
US5194614 reports the synthesis of (7-methoxy-1-naphthyl) acetonitrile, is directed to six reactions steps and obtains target compound, but the yield of its first step is relatively low, and poor reproducibility, do not meet the requirement of industrialized production.
Pharmacy value based on agomelatine and good market prospect, the effective ways finding the synthesis formula (I) that a kind of yield is good and controllability is strong are imperative.
Summary of the invention
Present invention solves the technical problem that it is to overcome the deficiencies in the prior art, it is provided that the preparation method of a kind of (7-methoxy-1-naphthyl) acetonitrile.
It is an object of the invention to be achieved through the following technical solutions, comprise the following steps:
1) 7-methoxyl group-ALPHA-tetralone and cyanoacetic acid react generation formula (II) compound；
2) adding dimethyl sulfoxide in reaction vessel, formula (II) compound, palladium charcoal and molecular sieve, return stirring reacts 3-5 hour；
3) by reacting liquid filtering, gained filtrate extracts through toluene, concentrate drying, has both obtained (7-methoxy-1-naphthyl) acetonitrile.
The present invention is on the basis of prior art, and using molecular sieve and palladium charcoal is that (7-methoxy-1-naphthyl) acetonitrile prepared by catalyst, compared with prior art, substantially increases response speed and yield, and target product yield is up to 93%.The preparation method production cost of the present invention is low, is suitable to industrialized production, also helps the reduction of downstream product agomelatine cost simultaneously.
Detailed description of the invention
Embodiment 1:
In dry reaction bulb, add dimethyl sulfoxide 400mL and (7-methoxyl group-3,4-naphthyl) acetonitrile 200g (1.0mol), dissolving is stirred at room temperature；4A molecular sieve 20g and palladium charcoal (5%) 10g is added in above-mentioned solution, heating reflux reaction 4.5 hours, filtering reacting liquid, filter liquor toluene extracts, organic facies concentrate drying had both obtained (7-methoxy-1-naphthyl) acetonitrile 190g, yield 95%.
Embodiment described above only the preferred embodiment of the present invention is described; not the scope of the present invention is defined; on the premise of designing spirit without departing from the present invention; various deformation that technical scheme is made by those of ordinary skill in the art and improvement, all should fall in the protection domain that claims of the present invention determines.
Claims (1)
1. the method preparing (7-methoxy-1-naphthyl) acetonitrile, it is characterized in that formula (II) compound in the presence of a molecular sieve, react with hydrogenation catalyst, obtain formula (I) compound after filtering and solvent being evaporated off, separate in solid form after formula (I) compound recrystallization:
Described reaction is carried out in dimethyl sulfoxide；Described molecular sieve is 4A molecular sieve；Described hydrogenation catalyst is the palladium charcoal of 5%；Described catalyst amount is based on the weight of substrate, for the 5% of substrate weight.
Priority Applications (1)
| 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 |
Applications Claiming Priority (1)
| 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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| Publication Number | Publication Date |
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| CN103319370A CN103319370A (en) | 2013-09-25 |
| CN103319370B true 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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| CN103319370A (en) | 2013-09-25 |
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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. |
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