CN102766672A - Kinetic resolution method of chiral amine - Google Patents
Kinetic resolution method of chiral amine Download PDFInfo
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- CN102766672A CN102766672A CN2011101161929A CN201110116192A CN102766672A CN 102766672 A CN102766672 A CN 102766672A CN 2011101161929 A CN2011101161929 A CN 2011101161929A CN 201110116192 A CN201110116192 A CN 201110116192A CN 102766672 A CN102766672 A CN 102766672A
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- ethamine
- naphthyl
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Abstract
The invention discloses a kinetic resolution method of chiral amine, comprising the following steps of: adding chiral amine and acyl donor at the mol ratio of 1:0.5-3 into an organic solvent reaction system, adding lipase which accounts for 10-80 wt% of the weight of chiral amine, and reacting at the reaction temperature of 30-70 DEG C for 12-48 hours to obtain amide with the conversion rate of 50% and e.e value being greater than 99%. According to the invention, resolution of chiral amine can be mildly realized under the condition of enzyme catalysis; and simultaneously, the product has good optical purity, high yield and great application values.
Description
Invention field
The present invention relates to the kinetic resolution method, relate in particular to a kind of kinetic resolution method of Chiral Amine.
Background technology
The Chiral Amine of single configuration is one type of chiral drug synthetic intermediate commonly used, also can be used as chiral base simultaneously and is used for splitting multiple chiral acid.In industry, when preparing these optical homochiral amine, the fractionation of racemic modification remains a kind of most important, the most practical method because of its economy and feasibility.To 1-(1-naphthyl) ethamine and the present topmost method for splitting of 1-(2-naphthyl) ethamine then is to be that chiral selectors carries out chemistry and splits with D one tartrate.This method exists resolution yield not high, and optical purity of products is not high, and problem such as environmental pollution is big.
How under the situation that guarantees high optical purity, realize that Chiral Amine is efficient, green fractionation becomes the target that we make great efforts.
Summary of the invention:
The objective of the invention is to overcome the deficiency that exists on the present resolving chiral amine method, a kind of kinetic resolution method of Chiral Amine is provided.
The step of the kinetic resolution method of Chiral Amine is following:
The adding mol ratio is 1: 0.5～3 Chiral Amine and acry radical donor in the reaction system of organic solvent; Ratio with Chiral Amine massfraction 10%-80% adds lypase, reacts 12-48 hour, and temperature of reaction is 30～70 ℃; Obtaining transformation efficiency is 50%, the acid amides of e.e value＞99%.
Described lypase is Novozyme 435; Chiral Amine is 1-(1-naphthyl) ethamine, 1-(2-naphthyl) ethamine; Described organic solvent is toluene, ETHYLE ACETATE, THF, methylene dichloride, chloroform, methyl alcohol; Described acry radical donor is a S-styroyl alcohol acetic ester, R-styroyl alcohol acetic ester.
Among the present invention, under the catalysis of enzyme, the transformation efficiency of Chiral Amine reaches 50%, and the e.e value of gained ester reaches＞and 99%, improved performance of products greatly, can satisfy various requirement to purity, reaction conditions is gentle simultaneously, has great using value.
Description of drawings
Fig. 1 is the liquid phase analysis figure of racemize 1-(1-naphthyl) ethamine;
Fig. 2 is the acetylate liquid phase analysis figure of racemize 1-(1-naphthyl) ethamine;
Fig. 3 is 1-(1-naphthyl) ethamine kinetic resolution process liquid phase analysis figure;
Embodiment
The adding mol ratio is 1: 0.5～3 Chiral Amine and acry radical donor in the reaction system of organic solvent; Ratio with Chiral Amine massfraction 10%-80% adds lypase, reacts 12-48 hour, and temperature of reaction is 30～70 ℃; Obtaining transformation efficiency is 50%, the acid amides of e.e value＞99%.
Described lypase is Novozyme 435; Chiral Amine is 1-(1-naphthyl) ethamine, 1-(2-naphthyl) ethamine; Described organic solvent be toluene, ETHYLE ACETATE,, THF, methylene dichloride, chloroform, methyl alcohol; Described acry radical donor is a S-styroyl alcohol acetic ester, R-styroyl alcohol acetic ester.
Among the present invention, under the catalysis of enzyme, the transformation efficiency of Chiral Amine reaches 50%, and the e.e value of gained ester reaches＞and 99%, improved performance of products greatly, can satisfy various requirement to purity, have great using value.
Embodiment 1
In the toluene solvant of Chiral Amine volume, adding mol ratio at 10 times is 1: 0.5 1-(1-naphthyl) ethamine and S-styroyl alcohol acetic ester; Ratio with 1-(1-naphthyl) ethamine massfraction 10% adds Novi's letter 435; Reacted 48 hours; Temperature of reaction is 30 ℃, and obtaining transformation efficiency is 50%, the R-1-acetonaphthone ethamine of e.e value＞99%.
Embodiment 2
In the toluene solvant of Chiral Amine volume, adding mol ratio at 10 times is 1: 3 1-(2-naphthyl) ethamine and S-styroyl alcohol acetic ester; Ratio with 1-(2-naphthyl) ethamine massfraction 80% adds Novi's letter 435; Reacted 12 hours; Temperature of reaction is 70 ℃, and obtaining transformation efficiency is 50%, the R-2-acetonaphthone ethamine of e.e value＞99%.
Embodiment 3
In the toluene solvant of Chiral Amine volume, adding mol ratio at 10 times is 1: 2 1-(1-naphthyl) ethamine and R-styroyl alcohol acetic ester; Ratio with 1-(1-naphthyl) ethamine massfraction 40% adds Novi's letter 435; Reacted 24 hours; Temperature of reaction is 70 ℃, and obtaining transformation efficiency is 50%, the S-1-acetonaphthone ethamine of e.e value＞99%.
Embodiment 4
In the ethyl acetate solvent of Chiral Amine volume, adding mol ratio at 10 times is 1: 2 1-(1-naphthyl) ethamine and R-styroyl alcohol acetic ester; Ratio with 1-(1-naphthyl) ethamine massfraction 40% adds Novi's letter 435; Reacted 24 hours; Temperature of reaction is 70 ℃, and obtaining transformation efficiency is 50%, the S-1-acetonaphthone ethamine of e.e value＞99%.
Embodiment 5
In the tetrahydrofuran solvent of Chiral Amine volume, adding mol ratio at 10 times is 1: 2 1-(1-naphthyl) ethamine and R-styroyl alcohol acetic ester; Ratio with 1-(1-naphthyl) ethamine massfraction 40% adds Novi's letter 435; Reacted 24 hours; Temperature of reaction is 70 ℃, and obtaining transformation efficiency is 50%, the S-1-acetonaphthone ethamine of e.e value＞99%.
Embodiment 6
In the chloroform solvent of Chiral Amine volume, adding mol ratio at 10 times is 1: 2 1-(1-naphthyl) ethamine and R-styroyl alcohol acetic ester; Ratio with 1-(1-naphthyl) ethamine massfraction 40% adds Novi's letter 435; Reacted 24 hours; Temperature of reaction is 70 ℃, and obtaining transformation efficiency is 50%, the S-1-acetonaphthone ethamine of e.e value＞99%.
Embodiment 7
In the dichloromethane solvent of Chiral Amine volume, adding mol ratio at 10 times is 1: 2 1-(1-naphthyl) ethamine and R-styroyl alcohol acetic ester; Ratio with 1-(1-naphthyl) ethamine massfraction 40% adds Novi's letter 435; Reacted 24 hours; Temperature of reaction is 70 ℃, and obtaining transformation efficiency is 50%, the S-1-acetonaphthone ethamine of e.e value＞99%.
Embodiment 8
In the methanol solvate of Chiral Amine volume, adding mol ratio at 10 times is 1: 2 1-(1-naphthyl) ethamine and R-styroyl alcohol acetic ester; Ratio with 1-(1-naphthyl) ethamine massfraction 40% adds Novi's letter 435; Reacted 24 hours; Temperature of reaction is 70 ℃, and obtaining transformation efficiency is 50%, the S-1-acetonaphthone ethamine of e.e value＞99%.
Embodiment 9
In the dichloromethane solvent of Chiral Amine volume, adding mol ratio at 10 times is 1: 2 1-(1-naphthyl) ethamine and R-styroyl alcohol acetic ester; Ratio with 1-(2-naphthyl) ethamine massfraction 40% adds Novi's letter 435; Reacted 24 hours; Temperature of reaction is 70 ℃, and obtaining transformation efficiency is 50%, the S-1-acetonaphthone ethamine of e.e value＞99%.
Embodiment 10
In the dichloromethane solvent of Chiral Amine volume, adding mol ratio at 10 times is 1: 2 1-(1-naphthyl) ethamine and S-styroyl alcohol acetic ester; Ratio with 1-(1-naphthyl) ethamine massfraction 40% adds Novi's letter 435; Reacted 24 hours; Temperature of reaction is 70 ℃, and obtaining transformation efficiency is 50%, the R-1-acetonaphthone ethamine of e.e value＞99%.
Claims (5)
1. the kinetic resolution method of a Chiral Amine is characterized in that its step is following:
The adding mol ratio is 1: 0.5～3 Chiral Amine and acry radical donor in the reaction system of organic solvent; Ratio with Chiral Amine massfraction 10%-80% adds lypase, reacts 12-48 hour, and temperature of reaction is 30～70 ℃; Obtaining transformation efficiency is 50%, the acid amides of e.e value＞99%.
2. the kinetic resolution method of a kind of Chiral Amine according to claim 1 is characterized in that, described lypase is Novozyme 435.
3. the kinetic resolution method of a kind of Chiral Amine according to claim 1 is characterized in that, described Chiral Amine is 1-(1-naphthyl) ethamine, 1-(2-naphthyl) ethamine.
4. the kinetic resolution method of a kind of Chiral Amine according to claim 1 is characterized in that, described organic solvent is toluene, ETHYLE ACETATE, THF, methylene dichloride, chloroform, methyl alcohol.
5. the kinetic resolution method of a kind of Chiral Amine according to claim 1 is characterized in that, described acry radical donor is a S-styroyl alcohol acetic ester, R-styroyl alcohol acetic ester.
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104178545A (en) * | 2014-08-14 | 2014-12-03 | 陈永军 | Method for preparing optically-pure S-2-naphthylethylamine through resolution |
| CN104263801A (en) * | 2014-09-17 | 2015-01-07 | 王际宽 | Preparation method of R-2-tetrahydronaphthylamine |
| CN104263803A (en) * | 2014-09-18 | 2015-01-07 | 王际宽 | Method of preparing S-2-tetrahydronaphthalene amine by dynamic kinetic resolution |
| CN104263797A (en) * | 2014-09-12 | 2015-01-07 | 王际宽 | Preparation method of R-1-aminotetralin |
| CN104263796A (en) * | 2014-09-12 | 2015-01-07 | 王际宽 | Preparation method of R-1-aminotetralin |
| CN104263800A (en) * | 2014-09-17 | 2015-01-07 | 王际宽 | Preparation method of S-2-tetrahydronaphthylamine |
| CN104263802A (en) * | 2014-09-18 | 2015-01-07 | 王际宽 | Preparation of S-1-tetralin amine employing dynamic kinetic resolution |
| CN104262169A (en) * | 2014-09-17 | 2015-01-07 | 王际宽 | Preparation method of R-2-tetrahydronaphthylamine |
| CN108368103A (en) * | 2015-10-18 | 2018-08-03 | 肿瘤治疗有限责任公司 | Adjust the composition and method of cancer related disorders and disease |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1177382A (en) * | 1995-03-02 | 1998-03-25 | 拜尔公司 | Process for preparing optically active amines |
-
2011
- 2011-05-06 CN CN2011101161929A patent/CN102766672A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1177382A (en) * | 1995-03-02 | 1998-03-25 | 拜尔公司 | Process for preparing optically active amines |
Non-Patent Citations (2)
| Title |
|---|
| ANDREI N. PARVULESCU, ET AL.: "Palladium Catalysts on Alkaline-Earth Supports for Racemization and Dynamic Kinetic Resolution of Benzylic Amines", 《CHEM. EUR. J.》, vol. 13, no. 7, 31 December 2007 (2007-12-31), pages 2034 - 2043 * |
| 张中义: "脂肪酶在手性药物制备中的应用", 《食品与药品》, vol. 9, no. 7, 30 September 2007 (2007-09-30), pages 40 - 43 * |
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104178545A (en) * | 2014-08-14 | 2014-12-03 | 陈永军 | Method for preparing optically-pure S-2-naphthylethylamine through resolution |
| CN104178545B (en) * | 2014-08-14 | 2016-12-07 | 六安佳诺生化科技有限公司 | The method of optical voidness S-2-naphthalene ethylamine is prepared in a kind of fractionation |
| CN104263797A (en) * | 2014-09-12 | 2015-01-07 | 王际宽 | Preparation method of R-1-aminotetralin |
| CN104263796A (en) * | 2014-09-12 | 2015-01-07 | 王际宽 | Preparation method of R-1-aminotetralin |
| CN104263797B (en) * | 2014-09-12 | 2017-12-19 | 六安佳诺生化科技有限公司 | The preparation of the tetrahydro naphthylamines of R 1 |
| CN104263800A (en) * | 2014-09-17 | 2015-01-07 | 王际宽 | Preparation method of S-2-tetrahydronaphthylamine |
| CN104262169A (en) * | 2014-09-17 | 2015-01-07 | 王际宽 | Preparation method of R-2-tetrahydronaphthylamine |
| CN104262169B (en) * | 2014-09-17 | 2016-01-06 | 王际宽 | The preparation of R-2-tetrahydro naphthylamine |
| CN104263801A (en) * | 2014-09-17 | 2015-01-07 | 王际宽 | Preparation method of R-2-tetrahydronaphthylamine |
| CN104263801B (en) * | 2014-09-17 | 2018-09-11 | 六安佳诺生化科技有限公司 | A kind of preparation method of R-2- tetrahydronaphthalene amines |
| CN104263800B (en) * | 2014-09-17 | 2018-09-14 | 六安佳诺生化科技有限公司 | The preparation method of S-2- tetrahydronaphthalene amines |
| CN104263803A (en) * | 2014-09-18 | 2015-01-07 | 王际宽 | Method of preparing S-2-tetrahydronaphthalene amine by dynamic kinetic resolution |
| CN104263802A (en) * | 2014-09-18 | 2015-01-07 | 王际宽 | Preparation of S-1-tetralin amine employing dynamic kinetic resolution |
| CN104263802B (en) * | 2014-09-18 | 2018-09-25 | 六安佳诺生化科技有限公司 | Dynamic Kinetic Resolution prepares S-1- tetrahydronaphthalene amines |
| CN108368103A (en) * | 2015-10-18 | 2018-08-03 | 肿瘤治疗有限责任公司 | Adjust the composition and method of cancer related disorders and disease |
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Application publication date: 20121107 |