CN105002257A - Preparation method of S-6-hydroxyl-1-aminoindane - Google Patents

Preparation method of S-6-hydroxyl-1-aminoindane Download PDF

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Publication number
CN105002257A
CN105002257A CN201510521090.3A CN201510521090A CN105002257A CN 105002257 A CN105002257 A CN 105002257A CN 201510521090 A CN201510521090 A CN 201510521090A CN 105002257 A CN105002257 A CN 105002257A
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hydroxyl
aminoidan
preparation
aminoindane
reaction
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陈永军
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陈永军
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Abstract

The invention discloses a method for preparing S-6-hydroxyl-1-aminoindane with dynamic kinetic resolution. The method comprises steps as follows: 6-hydroxyl-1-aminoindane is taken as a raw material, Candida antarctica lipase B is taken as a resolution catalyst, S-1-methyl benzyl alcohol acetate is taken as an acyl donor, raney nickel is taken as a racemization catalyst, hydrogen gas is introduced into a high-pressure kettle for reaction, and 6-hydroxyl-1-aminoindane is completely transformed into an acetyl compound of S-6-hydroxyl-1-aminoindane; a reaction product is subjected to purification, acidolysis and the like, S-6-hydroxyl-1-aminoindane salt is obtained, the salt is subjected to alkalization, extraction, drying, concentration and the like, S-6-hydroxyl-1-aminoindane is obtained, and the ee value of the product is higher than 99%. The preparation method has the characteristics of cheap and available racemization catalyst, complete utilization of the raw material, high optical purity of the product and the like, and has great guidance and application value in production and preparation of S-6-hydroxyl-1-aminoindane.

Description

S-6-hydroxyl-1-aminoidan preparation method
Technical field
The present invention relates to a kind of fractionation preparation method of optical homochiral compound, particularly relate to a kind of method that Dynamic Kinetic Resolution prepares S-6-hydroxyl-1-aminoidan.
Background technology
Indene compound can be used as the intermediate of medicine and agricultural chemicals, recent years, and domestic outgoing has opened the series compound medicine and the veterinary drug that with indenes are much parent.S-6-hydroxyl-1-aminoidan, as wherein a kind of important chiral medicinal intermediate, in existing 6-hydroxyl-1-aminoidan relevant report, then rarely has report about how preparing optical purity S-6-hydroxyl-1-aminoidan.Can be found by Research Literature, utilize kinetics and Dynamic Kinetic Resolution to prepare S type compound, be all a technical barrier for any product.The present invention with lipase candida antarctica lipase B for split catalyzer; Raney's nickel is racemization catalyst; be that acry radical donor successfully achieves Dynamic Kinetic Resolution and prepares S-6-hydroxyl-1-aminoidan by selecting S-1-styroyl alcohol acetic ester; and final product is S configuration; and the finished product yield is good, purity is high.
Summary of the invention
The technical problem to be solved in the present invention utilizes lipase candida antarctica lipase B for splitting catalyzer, and Raney's nickel is racemization catalyst, and how the Dynamic Kinetic Resolution of high yield, highly selective prepares S-6-hydroxyl-1-aminoidan.
In order to solve the problem, the invention provides a kind of method that Dynamic Kinetic Resolution prepares S-6-hydroxyl-1-aminoidan: 1) in autoclave, take toluene as solvent, the ratio of 1:1.0-2.0 adds 6-hydroxyl-1-aminoidan and acry radical donor S-1-styroyl alcohol acetic ester in molar ratio, lipase candida antarctica lipase B and Raney's nickel is added again in the ratio of raw material 6-hydroxyl-1-aminoidan massfraction 1%-10%, after autoclave sealing nitrogen replacement, pass into hydrogen to pressure 1.0-2.0MPa and be warming up to 40-75 DEG C reaction 8-20 hour, 6-hydroxyl-1-aminoidan can be converted into completely the acetyl compounds of S-6-hydroxyl-1-aminoidan, and product ee value reaches more than 99%, after reaction terminates, solution is concentrated, column chromatography, obtain the acetyl compounds of pure S-6-hydroxyl-1-aminoidan, 2) step 1 gained S-6-hydroxyl-1-aminoidan acetyl compound is dissolved in certain volume than in the alcohol of preparation and the mixing solutions of acid solution, under nitrogen protection condition, heating reflux reaction certain hour, S-6-hydroxyl-1-aminoidan acetyl compound complete hydrolysis obtains S-6-hydroxyl-1-aminoidan salt, 3) step 2 gained S-6-hydroxyl-1-aminoidan salt is carried out alkalinisation treatment, then by organic solvent extraction, drying, concentrated can obtain optically pure S-6-hydroxyl-1-aminoidan, the finished product purity can reach more than 99%.
The present invention utilizes common raw material successfully to achieve to prepare S-6-hydroxyl-1-aminoidan and hydrochloride thereof by Dynamic Kinetic Resolution, also possess that racemization catalyst is cheap and easy to get simultaneously, prepared using completely, optical purity of products high.In the manufacture of S-6-hydroxyl-1-aminoidan, have and instruct greatly and using value.
Specific implementation method:
Embodiment 1
1,6-hydroxyl-1-aminoidan is split
In 1000ML autoclave, add 500ML toluene, 74.5G6-hydroxyl-1-aminoidan, 90.2g S-1-styroyl alcohol acetic ester, 5g fold Candida lipase and 10g Raney's nickel, sealing autoclave, passes into hydrogen to pressure 1.5MP after air in still being carried out displacement with nitrogen in autoclave, open and stir, and be warming up to 45 DEG C and react; After 19 hours, sampling detects, and 6-hydroxyl-1-aminoidan is converted into the acetyl compounds of S-6-hydroxyl-1-aminoidan completely; After reaction terminates, concentrated by solution, column chromatography, obtain the acetyl compounds 70.1g of pure S-6-hydroxyl-1-aminoidan, yield is 91.1%.
2, acidolysis obtains S-6-hydroxyl-1-aminoidan salt
Get and repeat the acetyl compounds 95.5g of S-6-hydroxyl-1-aminoidan that previous step obtains several times and join in the solution that the ethanol of 1000ml and concentrated hydrochloric acid mix with volume ratio 1:1; pass into nitrogen protection; then reflux; react after 9 hours, the acetyl compounds complete hydrolysis that some plate detects S-6-hydroxyl-1-aminoidan obtains S-6-hydroxyl-1-aminoidan hydrochloride.
3, alkalization obtains S-6-hydroxyl-1-aminoidan
The solution that up step gained reacts completely slowly drips sodium hydroxide solution, and stir, detect solution pH value to 12, stop adding sodium hydroxide solution, then add 300ML methylene dichloride, separatory, upper water liquid uses the dichloromethane extraction 3 times of 100mL again, carry out drying by extracting the dichloromethane solution anhydrous sodium sulphate obtained several times, concentrated to obtain S-6-hydroxyl-1-aminoidan 69.0g, yield is the ee value that 92.6%, HPLC detects the finished product is 99.5%.
Embodiment 2
1,6-hydroxyl-1-aminoidan is split
In 1000ML autoclave, add 500ML toluene successively, 74.5G6-hydroxyl-1-aminoidan, 100g S-1-styroyl alcohol acetic ester, 7g fold Candida lipase and 14g Raney's nickel, sealing autoclave, with nitrogen, air in still is replaced, then in autoclave, pass into hydrogen to pressure 1.5MP, open and stir, and be warming up to 70 DEG C and react; After 11 hours, sampling detects, and 6-hydroxyl-1-aminoidan is converted into the acetyl compounds of S-6-hydroxyl-1-aminoidan completely; After reaction terminates, concentrated by solution, column chromatography, obtain the acetyl compounds 90.5g of S-6-hydroxyl-1-aminoidan, yield is 94.7%.
2, acidolysis obtains S-6-hydroxyl-1-aminoidan salt
Get and repeat the acetyl compounds 95.5g of S-6-hydroxyl-1-aminoidan that previous step obtains several times and join in the solution that the ethanol of 1000ml and the vitriol oil mix with volume ratio 2:1; pass into nitrogen protection; then reflux; react after 10 hours, the acetyl compounds complete hydrolysis that some plate detects S-6-hydroxyl-1-aminoidan obtains S-6-hydroxyl-1-aminoidan vitriol.
3, alkalization obtains S-6-hydroxyl-1-aminoidan
The solution that up step gained reacts completely slowly drips ammonia soln, and stir, detect solution pH value to 12, stop adding ammonia soln, then add 300ML ethyl acetate, separatory, lower layer of water liquid uses the extraction into ethyl acetate 3 times of 100mL again, carry out drying by extracting the ethyl acetate solution anhydrous sodium sulphate obtained several times, concentrated to obtain S-6-hydroxyl-1-aminoidan 68.2g, yield is the ee value that 91.6%, HPLC detects the finished product is 99.6%.

Claims (6)

  1. The preparation method of 1.S-6-hydroxyl-1-aminoidan is characterized in that: 1) in autoclave, take toluene as solvent, the ratio of 1:1.0-2.0 adds 6-hydroxyl-1-aminoidan and acry radical donor S-1-styroyl alcohol acetic ester in molar ratio, lipase candida antarctica lipase B and racemization catalyst Raney's nickel is added again in the ratio of raw material 6-hydroxyl-1-aminoidan massfraction 1%-10%, after autoclave sealing nitrogen replacement, pass into hydrogen to pressure 1.0-2.0MPa and be warming up to 40-75 DEG C reaction 8-20 hour, 6-hydroxyl-1-aminoidan can be converted into completely the acetyl compounds of S-6-hydroxyl-1-aminoidan, after reaction terminates, solution is concentrated, column chromatography, obtain the acetyl compounds of pure S-6-hydroxyl-1-aminoidan, 2) step 1 gained S-6-hydroxyl-1-aminoidan acetyl compound is dissolved in certain volume than in the alcohol of preparation and the mixing solutions of acid solution, under nitrogen protection condition, heating reflux reaction certain hour, S-6-hydroxyl-1-aminoidan acetyl compound complete hydrolysis obtains S-6-hydroxyl-1-aminoidan salt, 3) step 2 gained S-6-hydroxyl-1-aminoidan salt is carried out alkalinisation treatment, then with organic solvent extraction, drying, concentrated can obtain optically pure S-6-hydroxyl-1-aminoidan, the finished product purity can reach more than 99%, according to described, its reaction equation is as follows:
  2. 2. the preparation method of S-6-hydroxyl-1-aminoidan according to claim 1, is characterized in that: step 1) in acry radical donor be S-1-styroyl alcohol acetic ester, the feed ratio of itself and the amino indenes of 1-is mol ratio 1:1 ~ 2.0.
  3. 3. the preparation method of S-6-hydroxyl-1-aminoidan according to claim 1, is characterized in that: step 1) in biological resolution enzyme be candida antarctica lipase B, in reaction system, add-on is the 1%-10% of the amino indenes quality of 1-.
  4. 4. the preparation method of S-6-hydroxyl-1-aminoidan according to claim 1, is characterized in that: step 1) in racemization catalyst be Raney's nickel, in reaction system, add-on is the 1%-10% of the amino indenes quality of 1-.
  5. 5. the preparation method of S-6-hydroxyl-1-aminoidan according to claim 1, is characterized in that: step 1) in pass into hydrogen pressure be 1.0-2.0MPa.
  6. 6. the preparation method of S-6-hydroxyl-1-aminoidan according to claim 1, is characterized in that: step 1) in temperature of reaction be 40-75 DEG C.
CN201510521090.3A 2015-08-24 2015-08-24 Preparation method of S-6-hydroxyl-1-aminoindane Pending CN105002257A (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104151169A (en) * 2014-08-14 2014-11-19 陈永军 Method for resolution preparation of optically pure S-1-phenylethylamine
CN104152525A (en) * 2014-08-13 2014-11-19 陈永军 Resolution method for preparing optically pure R-1-phenylethylamine

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104152525A (en) * 2014-08-13 2014-11-19 陈永军 Resolution method for preparing optically pure R-1-phenylethylamine
CN104151169A (en) * 2014-08-14 2014-11-19 陈永军 Method for resolution preparation of optically pure S-1-phenylethylamine

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
丁奎岭 等: "《不对称催化新概念与新方法》", 28 February 2009, 化学工业出版社 *
戴晓庭 等: "动态动力学拆分制备(R)-1-氨基茚满", 《有机化学》 *
戴晓庭: "动态动力学拆分制备手性胺类化合物", 《中国优秀硕士学位论文全文数据库(电子期刊)工程科技I辑》 *
王雷 等: "动态动力学拆分制备手性化合物的研究进展", 《应用化工》 *
石贤爱 等: "Candida rugosa脂肪酶催化(R,S)-2-辛醇酯交换反应的对映选择性", 《华南理工大学学报(自然科学版)》 *
符思敏 等: "新型酰基供体用于酶法动力学拆分制备(R)-1-(2-萘基)乙胺的研究", 《有机化学》 *
陈永军: "化学酶法催化仲醇的动态动力学拆分", 《中国优秀硕士学位论文全文数据库(电子期刊)工程科技I辑》 *

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