CN104276956A - Method for preparing S-1-tetralin amine - Google Patents
Method for preparing S-1-tetralin amine Download PDFInfo
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- CN104276956A CN104276956A CN201410463579.5A CN201410463579A CN104276956A CN 104276956 A CN104276956 A CN 104276956A CN 201410463579 A CN201410463579 A CN 201410463579A CN 104276956 A CN104276956 A CN 104276956A
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- tetrahydro naphthylamine
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Abstract
The invention relates to a method for preparing S-1-tetralin amine by employing dynamic kinetic resolution. The method comprises the following steps: with 1-tetralin amine (I) as a raw material, Novozym435 as a catalyst splitting catalyst, L-(+)-O-acetyl mandelic acid as an acyl donor and KT-02 (a nickel catalyst) as a despun catalyst, introducing hydrogen into a high-pressure kettle to split the 1-tetralin amine (I); completely transforming the 1-tetralin amine (I) into a compound II (ee value is 99%); purifying the compound II and then carrying out acid hydrolysis to obtain a compound III; and finally obtaining the product S-1-tetralin amine (IV) through the operations such as alkalization, extraction, drying and concentration on the compound III, wherein the product yield in each step can reach over 90%, and the ee value is greater than 99%. The method has the characteristics that the catalyst is cheap and available, raw materials are completely utilized, the product yield is high, and the optical purity is high, thus the method has great guidance and application value in production and preparation of the S-1-tetralin amine.
Description
Technical field
The present invention relates to a kind of preparation method of optical homochiral amine, particularly relate to the Dynamic Kinetic Resolution preparation method of optical purity S-1-tetrahydro naphthylamine.
Background technology
S-1-tetrahydro naphthylamine, as important medicinal intermediates, has a wide range of applications in new drug synthesis field.In recent years, the great interest of medicament research and development personnel is caused.
At present, prepare S-1-tetrahydro naphthylamine and generally adopt first preparation 1-tetrahydro naphthylamine racemic modification (USP2001003136.2001-07-07; The method again split Bio.Med.Chem.2004.12 (15): 4189-4196), but there is the low problem of raw material availability in this method for splitting.Also (the J.Org.Chem.2006.71.6859-6862 adopting asymmetric catalysis to obtain optical purity 1-tetrahydro naphthylamine is had; Tetrahedron Asym.1998.9,4369-4379), but this method is prepared S-1-tetrahydro naphthylamine and not only be there is the low problem of product yield, also there is the problem that optical purity of products is not high.As for how utilizing Enzymatic Resolution to prepare S-1-tetrahydro naphthylamine then rarely seen report, utilize Enzymatic Resolution to prepare S-1-tetrahydro naphthylamine even if having, also needing to produce specific enzymes by bacterial screening could realize.
Summary of the invention
The technical problem to be solved in the present invention utilizes common lipase, and the racemization catalyst be easy to get successfully realizes Dynamic Kinetic Resolution and prepares S-1-tetrahydro naphthylamine.
In order to solve the problem, the invention provides a kind of preparation method of optical purity S-1-tetrahydro naphthylamine: 1) in autoclave, take toluene as solvent, the ratio of 1:1.0-2.0 adds raw material 1-tetrahydro naphthylamine and acry radical donor L-(+)-O-ethanoyl amygdalic acid in molar ratio, then lipase Novozym 435 and KT-02 is added in the ratio of 1-tetrahydro naphthylamine massfraction 1%-10%, after nitrogen replacement is carried out in autoclave sealing, pass into hydrogen to pressure 0.1-1.0MPa and be warming up to 40-90 DEG C reaction 24 hours, 1-tetrahydro naphthylamine can be converted into compound ii completely, and product ee value reaches 99%, after reaction terminates, solution is concentrated, column chromatography, obtain compound ii sterling, 2) be dissolved in the alcohol of 10 times of volume ratios and the mixing solutions of acid solution (v/v=1:1) by compound ii sterling obtained in step 1, then heating reflux reaction 15 hours, compound ii complete hydrolysis obtains compound III, 3) step 2 gained compound III is carried out alkalinisation treatment, then by organic solvent extraction, drying, concentrated can obtain optically pure S-1-tetrahydro naphthylamine (IV), final whole step product yield can reach more than 90%, and optical purity of products is 99%.
The present invention is in preparation S-1-tetrahydro naphthylamine process, and use Novozym 435 simple and easy to get as fractionation catalyzer, use KT-02 as racemization catalyst, cheap and easy to get, catalytic efficiency is good, and in whole split process, product yield is high, and optical purity is good.Possess above advantage, the present invention, in the production and preparation process of S-1-tetrahydro naphthylamine, possesses and instructs greatly and using value.
Specific implementation method:
1) compound ii is prepared in fractionation
1000mL toluene is added as solvent in the autoclave of 2000mL, add 117.6g1-tetrahydro naphthylamine, 172g L-(+)-O-ethanoyl amygdalic acid successively, 10g lipase Novozym 435 and 12gKT-02, after adding, with nitrogen, air in still is replaced after sealing autoclave, then in autoclave, pass into hydrogen to pressure 1.0MP, open and stir, and be warming up to 75 DEG C and react; After 30 hours, sampling detects, and 1-tetrahydro naphthylamine disappears and is converted into compound ii completely, and product II ee value 99.7%; After reaction terminates, concentrated by solution, be then that the normal hexane of 10:1 and alcohol mixed solvent carry out column chromatography by volume ratio, obtain pure compound II 142.4G, yield is 94.2%.
2) compound III acidolysis obtains compound III
Compound ii 94.6g obtained in upper step is joined in the solution that the ethanol of 1000ml and concentrated hydrochloric acid mix with volume ratio 1:1, reflux, after when reacting 8, put plate detection compound III complete hydrolysis and obtain compound III.
3) alkalization obtains S-1-tetrahydro naphthylamine (IV)
The solution that past step 2 gained reacts completely adds the methylene dichloride of 500mL, then slowly sodium hydroxide solution is dripped, rapid stirring, detect solution pH value to 13, stop dripping sodium hydroxide solution, separatory, upper water liquid uses the dichloromethane extraction 3 times of 200mL again, carry out drying by extracting the dichloromethane solution anhydrous sodium sulphate obtained several times, concentrated to obtain S-1-tetrahydro naphthylamine (V) 68.1g, yield is the ee value that 92.6%, HPLC detects the finished product is 99.3%.
Claims (4)
1. the preparation method of optical purity S-1-tetrahydro naphthylamine is characterized in that: 1) in autoclave, take toluene as solvent, the ratio of 1:1.0-2.0 adds raw material 1-tetrahydro naphthylamine and acry radical donor L-(+)-O-ethanoyl amygdalic acid in molar ratio, then lipase Novozym 435 and KT-02(ni-type catalyzer is added in the ratio of 1-tetrahydro naphthylamine massfraction 1%-10%), after nitrogen replacement is carried out in autoclave sealing, pass into hydrogen to pressure 0.1-1.0MPa and be warming up to 40-90 DEG C reaction 24 hours, 1-tetrahydro naphthylamine can be converted into compound ii completely, and product ee value reaches 99%, after reaction terminates, solution is concentrated, column chromatography, obtain compound ii sterling, 2) be dissolved in the alcohol of 10 times of volume ratios and the mixing solutions of acid solution (v/v=1:1) by compound ii sterling obtained in step 1, then heating reflux reaction 15 hours, compound ii complete hydrolysis obtains compound III, 3) step 2 gained compound III is carried out alkalinisation treatment, then by organic solvent extraction, drying, concentrated can obtain optically pure S-1-tetrahydro naphthylamine (IV), final whole step product yield can reach more than 90%, and optical purity of products is 99%, according to described, its reaction equation is as follows:
2. according to claim 1, the preparation method of optical purity S-1-tetrahydro naphthylamine is characterized in that step 1) in acry radical donor be L-(+)-O-ethanoyl amygdalic acid, racemization catalyst is KT-02.
3. according to claim 1, the preparation method of optical purity S-1-tetrahydro naphthylamine is characterized in that step 2) in alcohol be methyl alcohol or ethanol; Acid is hydrochloric acid or sulfuric acid.
4. according to claim 1, the preparation method of optical purity S-1-tetrahydro naphthylamine is characterized in that step 3) in alkalinisation treatment alkali used be sodium hydroxide, potassium hydroxide or ammoniacal liquor; Extracting organic solvent used is toluene, methylene dichloride, 1,2-ethylene dichloride, ether etc.
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| CN201410463579.5A CN104276956B (en) | 2014-09-12 | 2014-09-12 | A kind of preparation method of S-1-tetrahydro naphthylamine |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105018560A (en) * | 2015-08-13 | 2015-11-04 | 陈永军 | Method for preparing (S)-6-methoxy-1-aminoindane through dynamic kinetic resolution |
| CN106397218A (en) * | 2016-09-04 | 2017-02-15 | 王际菊 | S-alpha-cyclohexyl benzene methanamine |
| CN106397217A (en) * | 2016-09-04 | 2017-02-15 | 王际菊 | Method for synthesizing dextral alpha-cyclohexylbenzylamine |
| CN106467476A (en) * | 2016-09-04 | 2017-03-01 | 王际菊 | A kind of synthetic method of left-handed amine compound |
| CN106480118A (en) * | 2016-09-04 | 2017-03-08 | 王际宽 | A kind of left-handed Chiral Amine |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102675123A (en) * | 2012-06-11 | 2012-09-19 | 上海朗泽生物医药科技有限公司 | Resolving and racemization method for 1-amino-1,2,3,4-tetrahydronaphthalene |
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- 2014-09-12 CN CN201410463579.5A patent/CN104276956B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102675123A (en) * | 2012-06-11 | 2012-09-19 | 上海朗泽生物医药科技有限公司 | Resolving and racemization method for 1-amino-1,2,3,4-tetrahydronaphthalene |
Non-Patent Citations (3)
| Title |
|---|
| ANDREI N. PARVULESCU, ET AL.: "Palladium Catalysts on Alkaline-Earth Supports for Racemization and Dynamic Kinetic Resolution of Benzylic Amines", 《CHEM. EUR. J》 * |
| KRYSTYNA A. SKUPINSKA, ET AL.: "Enzymatic Resolution of Bicyclic 1-Heteroarylamines Using Candida antarctica Lipase B", 《J. ORG. CHEM.》 * |
| MARI PÄIVIÖ, ET AL.: "Solvent-free kinetic resolution of primary amines catalyzed by Candida antarctica lipase B: effect of immobilization and recycling stability", 《TETRAHEDRON: ASYMMETRY》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105018560A (en) * | 2015-08-13 | 2015-11-04 | 陈永军 | Method for preparing (S)-6-methoxy-1-aminoindane through dynamic kinetic resolution |
| CN105018560B (en) * | 2015-08-13 | 2018-09-14 | 陈永军 | Dynamic Kinetic Resolution prepares (S) -6- methoxyl group -1- aminoidans |
| CN106397218A (en) * | 2016-09-04 | 2017-02-15 | 王际菊 | S-alpha-cyclohexyl benzene methanamine |
| CN106397217A (en) * | 2016-09-04 | 2017-02-15 | 王际菊 | Method for synthesizing dextral alpha-cyclohexylbenzylamine |
| CN106467476A (en) * | 2016-09-04 | 2017-03-01 | 王际菊 | A kind of synthetic method of left-handed amine compound |
| CN106480118A (en) * | 2016-09-04 | 2017-03-08 | 王际宽 | A kind of left-handed Chiral Amine |
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Effective date of registration: 20160426 Address after: 237000 Anhui Province, Lu'an City Economic Development Zone West Lu'an gatever PI Biochemical Technology Co. Ltd. Patentee after: Liuan Jianuo Biochemical Technology Co.,Ltd. Address before: 237364 Anhui County of Jinzhai city of Lu'an Province Tang Jiahui Town Center School Patentee before: Wang Jikuan |
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Effective date of registration: 20161214 Address after: 237364 Anhui County of Jinzhai city of Lu'an Province Tang Jiahui Town Center School Patentee after: Wang Jikuan Address before: 237000 Anhui Province, Lu'an City Economic Development Zone West Lu'an gatever PI Biochemical Technology Co. Ltd. Patentee before: Liuan Jianuo Biochemical Technology Co.,Ltd. |
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