Preparation method and application of para-toluenesulfonate

A technology of methoxyphenyl and methyl, applied in the field of preparation and application of p-toluenesulfonate, can solve the problems of only 64% yield, increased production cost and high price

Inactive Publication Date: 2015-06-24
BEIJING LABWORLD BIO MEDICINE TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method overcomes the shortcomings of the above two routes, is simple to operate, and has a high yield. -Methyl-1-propanone, the reaction time is long, and the yield is only 64%
And in the steps of acylation, hydrogenolysis and deesterification, the price of raw materials 2-methyltetrahydrofuran and trifluoroacetic anhydride is relatively high, which increases the production cost, and the total yield of the two-step reaction only reaches 71%.

Method used

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  • Preparation method and application of para-toluenesulfonate
  • Preparation method and application of para-toluenesulfonate
  • Preparation method and application of para-toluenesulfonate

Examples

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Effect test

Embodiment 1

[0027] Example 1 Preparation of p-toluenesulfonate of (2S, 3R)-1-dimethylamino-3-(3-methoxyphenyl)-2-methyl-3-pentanol

[0028] Add 20g (2S, 3R)-1-dimethylamino-3-(3-methoxyphenyl)-2-methyl-3-pentanol to a 500ml round bottom flask, dissolve in 220ml tetrahydrofuran, and slowly Add 12.8g methanesulfonyl chloride and 16.6g triethylamine, after the reaction is complete, filter, add water, extract with dichloromethane, combine the organic layers, wash with water, wash with saturated brine, dry over magnesium sulfate, concentrate under reduced pressure and evaporate to dryness to obtain 27.1g of Yellow liquid, yield 98%.

Embodiment 2

[0029] Example 2 Preparation of (2R, 3R)-3-(3-methoxyphenyl)-N,N,2-trimethylpentylamine

[0030] Add 20g (2S, 3R)-1-dimethylamino-3-(3-methoxyphenyl)-2-methyl-3-pentanol to a 500ml round bottom flask, dissolve in 220ml tetrahydrofuran, and slowly Add 12.8g methanesulfonyl chloride and 16.6g triethylamine, after the reaction is complete, add 0.7g of 10% palladium carbon, nitrogen replacement 3 times, hydrogen replacement 3 times, under 10 bar pressure, reaction temperature 45 ℃, hydrogenation reaction for 12 hours . Filter, concentrate under reduced pressure, adjust pH=9-10 with sodium carbonate aqueous solution, extract with dichloromethane, combine organic layers, wash with water, wash with saturated brine, dry over magnesium sulfate, and concentrate under reduced pressure to obtain 18.3 g of light yellow liquid, yield 90%.

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Abstract

The invention relates to a preparation method of para-toluenesulfonate of (2S,3S)-dimethylamino-3-(3-methoxyphenyl)-2-methyl-3-amyl alcohol, represented by molecular formula I, and an application of the above compound in the preparation of tapentadol. Tapentadol is an analgesic with dual efficacies, is mu type opioid receptor stimulant, and also is a norepinephrine reabsorption inhibitor.

Description

technical field [0001] The present invention relates to the preparation method of the p-toluenesulfonate of (2S, 3R)-1-dimethylamino-3-(3-methoxyphenyl)-2-methyl-3-pentanol, see molecular formula I, Hereinafter referred to as p-toluenesulfonate, [0002] [0003] It also relates to the application of the compound as an intermediate in preparing tapentadol, an analgesic with dual functions of mu opioid receptor agonist and norepinephrine reabsorption inhibitor. Background technique [0004] European patent EP0693475 discloses 1-phenyl-3-dimethylaminopropane active compounds with excellent analgesic activity and very good tolerance, especially tapentadol, the structural formula is as shown in formula (Ⅴ), [0005] [0006] Tapentadol is a central analgesic with a dual mechanism of action developed by Johnson & Johnson. It is both a mu-type opioid receptor agonist and a norepinephrine reuptake inhibitor. The first single-molecule drug that possesses the above two pharma...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C309/73C07C303/28C07C217/62C07C215/54C07C213/08
Inventor 温光辉宛六一张典鹏
Owner BEIJING LABWORLD BIO MEDICINE TECH
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