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Preparation method of tapentadol intermediate

A technology for tapentadol and intermediates, which is applied in the field of preparation of pharmaceutical intermediates, and can solve problems such as difficult large-scale application, low utilization rate of raw materials, and increased costs

Active Publication Date: 2017-05-17
YIBIN JIULING CHEM
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

But this method is difficult to carry out large-scale application in industrial production, and the purity of the final product is not high
[0012] CN104803861 discloses a preparation method for synthesizing tapentadol hydrochloride, which directly obtains the desired chiral isomer through reaction through chiral catalysis. Although the method shortens the route, the utilization rate of raw materials is not high, increasing cost

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  • Preparation method of tapentadol intermediate

Examples

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Effect test

preparation Embodiment 1

[0049] (1) Take magnesium chips (0.1 mol) in a 100 mL round bottom flask, add a small amount of iodine, under nitrogen protection, add 10 mL of anhydrous tetrahydrofuran and 0.05 mol of the compound of formula (VI), react for 15 minutes, continue to dropwise add 0.095 mol of 80ml of anhydrous THF of the compound of formula (VI), until the end of the reaction, the Grignard reagent of the compound of formula (VI) is obtained. The Grignard reagent can also be prepared according to other methods in the prior art, which does not affect the spirit of the present invention.

[0050] (2) In a 100ml flask, add 0.01mmol of S-BINOL, under the protection of nitrogen, add 25ml of anhydrous tetrahydrofuran, dropwise add 0.05mmol of titanium tetraisopropoxide, and react for 60min. Add dropwise 1.5 mmol of the Grignard reagent synthesized in step (1) (dissolved in 30 ml of anhydrous tetrahydrofuran) under an ice bath, continue the reaction for 1.5 hours, and dropwise add 1.3 mmol of the compo...

preparation Embodiment 2

[0064] The pilot scale test was carried out according to the method described in Preparation Example 1, except that the addition of each raw material was increased to 1000 times that of the raw materials described in Preparation Example 1. Wherein the yield of step (2) is 80%, the yield of step (3) is 89%, the yield of step (4) is 90%, and the yield of step (5) is 82%. The single impurity of the compound of the obtained formula (I) is ≤0.14 wt%, and the total impurity is ≤0.2 wt%; after refining with ethanol-water, the content is ≥99%, which meets the requirements of the quality standard of this product in European Pharmacopoeia EP-7.0, and the total impurity<0.1 %.

[0065] The chromatographic detection conditions and method are the same as those in Preparation Example 1.

[0066] The invention has the following technical effects: the reactions in each step are preferably carried out at a relatively low temperature, the reaction conditions are mild, the synthesis of impuriti...

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Abstract

The invention relates to a preparation method of a tapentadol intermediate. A compound with a simple structure is taken as a raw reaction material to prepare 3-(dimethyl amino)-1-(3-methoxyphenyl)-2-methyl-1-acetone which is a tapentadol intermediate. The preparation method is mild in reaction condition, available in raw materials, high in yield of target products, and what's more, super high in product purity.

Description

technical field [0001] The present invention relates to a kind of preparation method of pharmaceutical intermediate, specifically, the present invention relates to a kind of preparation method of tapentadol intermediate. Background technique [0002] 1-phenyl-3-dimethylaminopropane active compounds with excellent analgesic activity and very good tolerance, especially tapentadol, the structure is shown in the following formula: [0003] [0004] The chemical name is (-)-(1R, 2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloric acid, which was launched in November 2008 and is manufactured by Gruenenthal, Germany A new type of central analgesic developed by the company with dual action modes of MOR (μ-opioid receptor) agonism and NE (norepinephrine) reuptake inhibition is used to relieve moderate to severe acute pain in the central nervous system of adults. [0005] The results of the study showed that tapentadol is effective in acute, inflammatory and chronic...

Claims

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Application Information

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IPC IPC(8): C07C221/00C07C225/16C07C217/62C07C247/10C07C217/72
CPCC07C213/00C07C213/02C07C217/62C07C217/72C07C221/00C07C225/16C07C247/10
Inventor 张国良方善伦贾云峰高福元袁晓波何红汤月鲜
Owner YIBIN JIULING CHEM
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