Preparation method of tasimelteon

A technology of tasimelteon and reducing agent, which is applied in the field of preparation of tasimelteon, can solve the problems of complexity, economical reduction, and long reaction steps, and achieve the effects of reducing reaction steps, improving utilization rate, and simple process

Inactive Publication Date: 2013-05-08
JINAN ZHIHE MEDICAL TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] The intermediate prepared by the above method must be further reacted with propionyl chloride to prepare tasimelteon, so the reaction steps are long and complicated, and the economy is reduced

Method used

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  • Preparation method of tasimelteon
  • Preparation method of tasimelteon
  • Preparation method of tasimelteon

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Add 2.0g of (1R,2R)-2-(2,3-dihydrobenzofuran-4-yl)cyclopropanecarboxamide and 1.9g of sodium borohydride to 40ml of anhydrous tetrahydrofuran and heat to reflux, where ( The molar ratio of 1R,2R)-2-(2,3-dihydrobenzofuran-4-yl)cyclopropanamide to sodium borohydride is about 1:5. Add 12.5g propionic acid and 20ml anhydrous slowly. The mixed solution of tetrahydrofuran (the molar ratio of sodium borohydride to propionic acid is about 1:3.3), add it in 12 hours, then continue the reaction at 70°C for about 6 hours, and then drop to room temperature. Pour the materials slowly into 100ml ice water and stir. Add dropwise about 20g of hydrochloric acid with a mass concentration of 10%, and adjust the pH to about 2. The obtained product was distilled under reduced pressure to remove the solvent tetrahydrofuran, and then extracted with 60 ml of dichloromethane. The aqueous phase was extracted once with 30 ml of dichloromethane. The organic phases were combined. The obtained organi...

Embodiment 2

[0036] In addition to adding 0.78g sodium borohydride and 2.8g propionic acid, the molar ratio of (1R,2R)-2-(2,3-dihydrobenzofuran-4-yl)cyclopropanamide to sodium borohydride is about The molar ratio of sodium borohydride to propionic acid is about 1:1.8. Tasmetron was prepared according to the same process as in Example 1, to obtain 1.79 g of white needle-shaped crystals of tasmetron with a purity of 98.7%. The rate is 85%.

Embodiment 3

[0038] In addition to adding 3.51g sodium borohydride and 35.1g propionic acid, the molar ratio of (1R,2R)-2-(2,3-dihydrobenzofuran-4-yl)cyclopropanamide to sodium borohydride is about The molar ratio of sodium borohydride to propionic acid is about 1:5. Tasmetron was prepared according to the same process as in Example 1, to obtain 2.3 g of white needle-shaped crystals of tasmetron with a purity of 99.9%. The rate is 94%.

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Abstract

The invention relates to a preparation method of tasimelteon. According to the method, (1R,2R)-2-(2,3-dihydrobenzofuran-4-yl) cyclopropanecarboxamide, a reducing agent and propionic acid are adopted to prepare the tasimelteon by a one-step method. The tasimelteon prepared by the method has high purity, and the preparation method is a one-step method, so that the preparation method is economical and efficient, and is advantageous to large-scale industrial production.

Description

Technical field [0001] The present invention relates to the field of chemical pharmacy, in particular to a method for preparing talsmetron, which uses (1R, 2R)-2-(2,3-dihydrobenzofuran-4-yl) Cyclopropanamide, reducing agent and propionic acid are prepared by a one-step method of tasmetron. Background technique [0002] Tasmetron, represented by the following formula 1, is a new type of oral melatonin receptor agonist, developed by Wanda Pharmaceuticals, Maryland, USA. It can simultaneously improve the sleep latency and sleep maintenance of people who suddenly sleep earlier, and has potential for treatment Transient insomnia in patients with day and night rhythm sleep disorders. [0003] [0004] Formula 1 [0005] The general method for synthesizing talsmetron in the prior art usually takes (1R, 2R)-2-(2,3-dihydrobenzofuran-4-yl)cyclopropylmethylamine represented by formula 2 as an intermediate to further interact with The reaction of propionyl chloride to synthesize talsmetron. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D307/79
Inventor 刘永志张宏川刘瑾
Owner JINAN ZHIHE MEDICAL TECH
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