CN104263799A - Preparation method of S-2-tetrahydronaphthylamine - Google Patents

Preparation method of S-2-tetrahydronaphthylamine Download PDF

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CN104263799A
CN104263799A CN201410474029.3A CN201410474029A CN104263799A CN 104263799 A CN104263799 A CN 104263799A CN 201410474029 A CN201410474029 A CN 201410474029A CN 104263799 A CN104263799 A CN 104263799A
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preparation
compound
tetrahydro naphthylamine
tetrahydronaphthylamine
optical purity
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CN104263799B (en
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王际宽
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王际宽
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Abstract

The invention relates to a dynamic kinetic resolution preparation method of S-2-tetrahydronaphthylamine. The preparation method comprises the steps of introducing hydrogen to a high-pressure kettle to resolve 2-tetrahydronaphthylamine (I) serving as a raw material by taking Novozym435 as a resolution catalyst, L-(+)-O-acetylmandelic acid as an acyl donor and KT-02 (a nickel catalyst) as a racemization catalyst, and completely converting 2-tetrahydronaphthylamine (I) to obtain a compound (II) (the ee value is 99%); and carrying out acidolysis after purifying the compound (II) to obtain a compound III, and carrying out alkalization, extraction, drying, concentration and other operations on the compound III to obtain a final product, namely S-2-tetrahydronaphthylamine (IV). The yields of products in all steps can be up to more than 90%, and the ee values of all the products are larger than 99%. The preparation method has the advantages that the catalyst is cheap and available, the raw material is completely utilized, and S-2-tetrahydronaphthylamine is high in yield and optical purity. The preparation method has great guide and application values in production and preparation of S-2-tetrahydronaphthylamine.

Description

A kind of preparation method of S-2-tetrahydro naphthylamine
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-2-tetrahydro naphthylamine.
Background technology
S-2-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-2-tetrahydro naphthylamine and generally adopt first preparation 2-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 2-tetrahydro naphthylamine is had; Tetrahedron Asym.1998.9,4369-4379), but this method is prepared S-2-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-2-tetrahydro naphthylamine then rarely seen report, utilize Enzymatic Resolution to prepare S-2-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-2-tetrahydro naphthylamine, and ensure that product has good yield and optical purity.
In order to solve the problem, the invention provides a kind of preparation method of optical purity S-2-tetrahydro naphthylamine: 1) in autoclave, take toluene as solvent, the ratio of 1:1.0-2.0 adds raw material 2-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 2-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 40-70 DEG C reaction 24 hours, 2-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-2-tetrahydro naphthylamine (IV), final each step product yield all can reach more than 90%, and optical purity of products is greater than 99%.
The present invention is in preparation S-2-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-2-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 117.6g2-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 2-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 137.3G, yield is 90.8%.
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-2-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-2-tetrahydro naphthylamine (V) 69.2g, yield is the ee value that 94.1%, HPLC detects the finished product is 99.5%.

Claims (4)

1. the preparation method of optical purity S-2-tetrahydro naphthylamine is characterized in that: 1) in autoclave, take toluene as solvent, the ratio of 1:1.0-2.0 adds raw material 2-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 2-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, 2-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-2-tetrahydro naphthylamine (IV), each step product yield can reach more than 90%, and optical purity is all greater than 99%, according to described, its reaction equation is as follows:
2. according to claim 1, the preparation method of optical purity S-2-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-2-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-2-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.
CN201410474029.3A 2014-09-17 2014-09-17 A kind of preparation method of S-2- tetrahydronaphthalene amines Active CN104263799B (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005014509A1 (en) * 2003-07-15 2005-02-17 Dsm Ip Assets B.V. Process for the preparation of enantiomerically enriched esters and alcohols
CN102392065A (en) * 2011-09-20 2012-03-28 浙江大学 Dynamic kinetic resolution method of 1-(1-naphthyl) ethylamine
CN102533922A (en) * 2011-12-14 2012-07-04 浙江大学 Method for catalyzing dynamic kinetic resolution of arylamine via racemization catalyst
CN102559792A (en) * 2011-09-20 2012-07-11 浙江大学 Method for enzymatic resolution of phenylethylamines by using novel acyl donor

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005014509A1 (en) * 2003-07-15 2005-02-17 Dsm Ip Assets B.V. Process for the preparation of enantiomerically enriched esters and alcohols
CN102392065A (en) * 2011-09-20 2012-03-28 浙江大学 Dynamic kinetic resolution method of 1-(1-naphthyl) ethylamine
CN102559792A (en) * 2011-09-20 2012-07-11 浙江大学 Method for enzymatic resolution of phenylethylamines by using novel acyl donor
CN102533922A (en) * 2011-12-14 2012-07-04 浙江大学 Method for catalyzing dynamic kinetic resolution of arylamine via racemization catalyst

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
ANDREI N. PARVULESCU,ET AL.: "Heterogeneous Raney Nickel and Cobalt Catalysts for Racemization and Dynamic Kinetic Resolution of Amines", 《ADV. SYNTH. CATAL.》 *
徐刚等: "有机相中酶催化1-苯基乙胺的不对称酰胺化反应", 《化工学报》 *

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