A kind of preparation method of r-1-aminoindane

An aminoindan and acyl technology, which is applied in the field of separation and preparation of optically pure chiral compounds, can solve the problems of low corresponding selectivity, high cost, low utilization rate of raw materials, etc., and achieves high optical purity, stable properties, and utilization of raw materials. full effect

Active Publication Date: 2018-11-09
陈永军
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  • Description
  • Claims
  • Application Information

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Problems solved by technology

Among the reported methods: the chemical asymmetric synthesis method has the disadvantages of low corresponding selectivity and high cost; the chemical resolution method and the kinetic resolution catalyzed by biological enzymes have the disadvantage of low raw material utilization

Method used

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  • A kind of preparation method of r-1-aminoindane

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Embodiment 1

[0007] 1. Resolution of 1-aminoindane

[0008] In a 1000ML autoclave, add 500ML toluene, 66.6G 1-aminoindan, 115.9g D-(-)-O-acetylmandelic acid, 4g Candida plicata lipase and 6g KT-02, seal the autoclave, and blow it with nitrogen After replacing the air in the autoclave, feed hydrogen into the autoclave to a pressure of 1.0MP, start stirring, and raise the temperature to 50°C for reaction; after 18 hours, take a sample and detect that 1-aminoindane is completely converted into R-1-amino Acetyl compound of indane; after the reaction, the solution was concentrated and subjected to column chromatography to obtain 84.1 g of acetyl compound of pure R-1-aminoindane with a yield of 96.1%.

[0009] 2. Acid hydrolysis to obtain R-1-aminoindan salt

[0010] Take several times to get 87.6g of the acetyl compound of R-1-aminoindane prepared in the previous step and add it to 1000ml of ethanol and concentrated hydrochloric acid in a volume ratio of 1:1, then heat to reflux and react for ...

Embodiment 2

[0014] 1. Resolution of 1-aminoindane

[0015] In a 1000ML autoclave, add 500ML toluene, 66.6G1-aminoindan, 144.9g D-(-)-O-acetylmandelic acid, 5g Candida plicata lipase and 10g KT-02 successively, seal the autoclave, and use Nitrogen replaced the air in the autoclave, then introduced hydrogen into the autoclave to a pressure of 1.5MP, started stirring, and raised the temperature to 70°C for reaction; after 14 hours, sampling and testing showed that 1-aminoindane was completely converted into R-1 - the acetyl compound of aminoindane; after the reaction, the solution was concentrated and subjected to column chromatography to obtain 82.9 g of the acetyl compound of R-1-aminoindane, with a yield of 94.7%.

[0016] 2. Acid hydrolysis to obtain R-1-aminoindan salt

[0017] Take 87.6g of the acetyl compound of R-1-aminoindane obtained by repeating the previous step several times and add it to the solution mixed with 1000ml of ethanol and concentrated sulfuric acid at a volume ratio...

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Abstract

The invention relates to a method for preparing R-1-aminoindan by using dynamic kinetic resolution. The method is as follows: using candida rugosa lipase as a biological resolution catalyst, D-(-)-O-acetyl mandelic acid as an acyl donor, and KT-02 as a racemic catalyst; in the presence of hydrogen and at a certain temperature, carrying out dynamic kinetic resolution on 1-aminoindan in an autoclave, so as to transform 1-aminoindan to an R-1-aminoindan acyl compound; carrying out acid hydrolysis on the acyl compound and treating using free alkali to obtain R-1-aminoindan with the optical purity of greater than 99%. The method has the characteristics that the operation is simple, the racemic catalyst is inexpensive and easy to get, the material is fully utilized, and the final product is high in optical purity; therefore, the method has great guidance and application values in the preparation of R-1-aminoindan.

Description

technical field [0001] The invention discloses a method for the resolution and preparation of optically pure chiral compounds, in particular to a method for preparing R-1-aminoindan by means of dynamic kinetic resolution. Background technique [0002] R-1-aminoindan is an important intermediate in the synthesis of rasagiline (US 5457133, 1995; US 5532415, 1996). Rasagiline is an irreversible and selective monoamine oxidase-B (MAO-B) inhibitor jointly developed by Teva Company of Israel and Lundbeck Company of Denmark. Phase III clinical research has been completed, and the drug was approved to be marketed in Europe in February 2005, and has received an approval letter from the US FDA. Compared with the similar drug, Selegiline, the drug has less side effects, higher efficacy and better selectivity, and is a promising new anti-Parkinson drug. As the key intermediate of rasagiline, R-1-aminoindan is currently obtained mainly by chemical asymmetric synthesis (Chin. J. Org. Ch...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P41/00C12P13/00
Inventor 陈永军
Owner 陈永军
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