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Method for preparing important intermediate of tapentadol hydrochloride analgesic

A tapentadol and intermediate technology, applied in the field of drug synthesis, can solve the problems of undesired cost economy and achieve the effect of reducing production cost

Inactive Publication Date: 2011-01-19
TIANJIN TAIPU PHARMA SCI & TECH DEV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Such methods have the disadvantage of disposing of enantiomers as waste chemicals, which is not cost-effective

Method used

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  • Method for preparing important intermediate of tapentadol hydrochloride analgesic
  • Method for preparing important intermediate of tapentadol hydrochloride analgesic
  • Method for preparing important intermediate of tapentadol hydrochloride analgesic

Examples

Experimental program
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Effect test

preparation Embodiment 1

[0025] Preparation of (2S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol hydrochloride

[0026]

[0027] Add 26.99 grams (1.11 moles) of magnesium chips and 105 milliliters of anhydrous tetrahydrofuran into a dry and anhydrous four-necked flask, and add dropwise 207.63 g (1.11 moles) of 3-bromoanisole dissolved in 400 milliliters of anhydrous tetrahydrofuran under stirring solution, the reaction is exothermic, and the reaction solution is slowly boiled. After the addition of the 3-bromoanisole solution was complete, the mixture was heated to reflux for 1 hour and then cooled to 5-10°C. A solution of 128.3 g (0.89 mol) of (S)-1-dimethylamino-2-methyl-3-pentanone dissolved in 400 ml of tetrahydrofuran was added at this temperature. The reaction solution was allowed to stand overnight at room temperature, and then cooled to 5-10°C. Ammonium chloride solution was added to decompose Grignard's solution. The reaction mixture was diluted with ethyl acetate, the organi...

preparation Embodiment 2

[0029] Preparation of (2S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol hydrochloride

[0030]

[0031]Add 26.99 grams (1.11 moles) of magnesium chips and 105 milliliters of anhydrous tetrahydrofuran into a dry and anhydrous four-necked flask, and add dropwise 280.6 grams (1.5 moles) of 3-bromoanisole dissolved in 400 milliliters of anhydrous tetrahydrofuran under stirring solution, the reaction is exothermic, and the reaction solution is slowly boiled. After the addition of the 3-bromoanisole solution was complete, the mixture was heated to reflux for 1 hour and then cooled to 5-10°C. A solution of 114.6 g (0.8 mol) of (S)-1-dimethylamino-2-methyl-3-pentanone dissolved in 400 ml of tetrahydrofuran was added at this temperature. The reaction solution was allowed to stand overnight at room temperature, and then cooled to 5-10°C. Ammonium chloride solution was added to decompose Grignard's solution. The reaction mixture was diluted with ethyl acetate, the organi...

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Abstract

The invention relates to a method for preparing an import intermediate of a tapentadol hydrochloride analgesic, which is (2S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentyl-3-ol hydrochloride. The (2S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentyl-3-ol hydrochloride with optical activity is obtained by the Grignard reaction of a compound II with optical activity and a compound III with optical activity. The Grignard reaction is performed by mixing magneson solution of the compound III and the tetrahydrofuran solution of the compound II at 5 to 10 DEG C and standing the mixed solution at room temperature overnight. The molar ratio of the compound II to the compound III is 0.8-1:1.0-1.5. The preparation method of the invention is not limited by a chiral column split instrument, solves the problem of processing enantiomers as waste chemicals, reduces production cost and is more suitable for large-batch industrial production.

Description

technical field [0001] The invention belongs to the technical field of drug synthesis, and relates to a preparation method of an important intermediate of tapentadol for treating moderate and severe acute pain. More specifically, it is a preparation method of (2S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol hydrochloride. Background technique [0002] Tapentadol (tapentadolhydrochloride) is a novel oral analgesic drug acting on the central nervous system developed by Johnson & Johnson Company of the United States. Emotional factors inhibit the transmission of pain in the spinal cord, thereby affecting and controlling the activity of the cerebral cortex that perceives pain; the other is the inhibitory effect on the reuptake of norepinephrine, inhibiting its reabsorption into nerve cells, thereby improving brain function. The level of norepinephrine in the blood also plays an analgesic effect. Tapentadol does not rely on metabolic activation and has no metabolic ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C217/72C07C213/08
Inventor 周学福魏文涛韩建萍瞿虹
Owner TIANJIN TAIPU PHARMA SCI & TECH DEV
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