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R-1-aminoindan preparation method

A technology of aminoindane and mandelic acid, which is applied in the purification/separation of amino compounds, organic chemistry, etc., can solve the problems of expensive resolution catalyst, troublesome post-processing, low selectivity, etc., and achieve good effect, reasonable selection, and resolution The effect of simple method

Inactive Publication Date: 2017-12-01
吴玲
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Among the several methods reported: the chemical asymmetric synthesis method has the disadvantages of low corresponding selectivity and high cost; the kinetic resolution catalyzed by biological enzymes has the disadvantages of expensive resolution catalyst and troublesome post-treatment.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0007] (1)

[0008] In a 1000ml round bottom flask, add 18.2G (0.12mol) L-mandelic acid to a mixed solution of methanol (200ml) and water (100ml), heat to 50°C, add 13.3G (0.1mol) of 1-aminoindane ), reflux reaction for 1.5 hours, cooled to room temperature, and filtered to obtain the crude product of L-mandelate salt of R-1-aminoindane. The resulting salt was added to a mixture of methanol (100ml) and water (50ml) for recrystallization to obtain 11.5g of L-mandelate salt of R-1-aminoindane.

[0009] (2)

[0010] Dissolve 11.5g of L-mandelate salt of R-1-aminoindane obtained in the previous step in 200ml of water, add dropwise 40% sodium hydroxide solution to adjust the pH value to 12, and extract with dichloromethane (100ml, 50ml, 50ml) Three times, the dichloromethane layers were combined, washed with water (50ml) and saturated brine (50ml) once each, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 4.8g of R-1-aminoindane with a yield of 36%, ee ...

Embodiment 2

[0014] (1)

[0015] In a 1000ml round bottom flask, add 22.8G (0.15mol) of L-mandelic acid into a mixed solution of ethanol (200ml) and water (200ml), heat to 50°C, add 13.3G (0.1mol) of 1-aminoindane ), reflux reaction for 1.0 hour, cooled to room temperature, and filtered to obtain the crude product of L-mandelate salt of R-1-aminoindane. The resulting salt was added to a mixture of ethanol (110ml) and water (40ml) for recrystallization to obtain 10.6g of L-mandelate salt of R-1-aminoindane.

[0016] (2)

[0017] Dissolve 10.6 g of L-mandelate salt of R-1-aminoindane obtained in the previous step in 300 ml of water, add ammonia water dropwise to adjust the pH value to 13, extract 3 times with ethyl acetate (100 ml, 50 ml, 50 ml), dichloro The methane layers were combined, washed once with water (50ml) and saturated brine (50ml), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 4.0g of R-1-aminoindane with a yield of 30% and an ee value of 99.4%.

...

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PUM

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Abstract

The invention discloses a splitting preparation method of R-1-aminoindan. According to the splitting preparation method, 1-aminoindan is used as a raw material, L-mandelic acid is used as a splitting agent, a reaction is performed in a suitable solvent to obtain 1-aminoindan L-mandelate, crystallization separation is performed to obtain R-1-aminoindan L-mandelate, and the R-1-aminoindan L-mandelate is subjected to re-crystallization and alkalization to obtain R-1-aminoindan, wherein the reaction and re-crystallization mother liquor is evaporated to remove the alcohol, the obtained liquid and other solutions containing the L-mandelate are mixed, and the obtained mixed solution is subjected to acidification, extraction with an organic solvent, concentration and other operations so as to recover the L-mandelic acid. According to the present invention, the method has advantages of mild conditions, simple operation, high product yield, high optical purity of the product, splitting agent recycling and the like, and is suitable for the industrial production of R-1-aminoindan.

Description

technical field [0001] The invention relates to a method for the resolution and preparation of optically pure chiral compounds, in particular to a method for the resolution and preparation of R-1-aminoindane. 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. Chem. 2002, 22,...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C211/42C07C209/88
Inventor 吴玲
Owner 吴玲