Preparation method of dexibuprofen

A technology of dexbuprofen and meglumine, which is applied in the field of preparation of dexbuprofen, can solve the problems of low melting point of dextro-amine salt, content of dextro-ibuprofen levorotate exceeding the qualified standard and the like, and achieves high molar yield Effect

Inactive Publication Date: 2019-12-27
HUBEI BIOCAUSE HEILEN PHARM CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the resolution ratio prepared by this reference document is high, according to the process conditions, the melting point of the prepared D-amine salt is seriously low, and the content of the L-isomer of Dexibuprofen after hydrolysis and acidification seriously exceeds the qualified standard

Method used

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  • Preparation method of dexibuprofen
  • Preparation method of dexibuprofen
  • Preparation method of dexibuprofen

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0017] A preparation method of Dexibuprofen, said method comprising:

[0018] 1. Preparation of amine salt:

[0019] 1. Put the amount of toluene (2448L) into the reaction kettle according to the feeding ratio, add about 50L hydrochloric acid solution (14-18%), stir for more than 10 minutes, let stand for more than 10 minutes, and divide the hydrochloric acid layer; then add about 200L For drinking water, stir for more than 10 minutes, let it stand for more than 10 minutes, and separate the water layer.

[0020] 2. Put in 315kg of ibuprofen and 216kg of octylglucamine according to the ratio, seal the hole cover, stir and heat up to 76-80°C, and keep it warm for more than 0.5 hours.

[0021] 3. Transfer the material to an amine salt crystallization kettle, add about 4.5L of purified water, and then cool down to crystallize. After the temperature drops to 18-22°C, put the material in a centrifuge to dry (10-15min), and then wash it with toluene 1 time (30~50L), rinse once (30~...

Embodiment 2

[0034] A preparation method of Dexibuprofen, said method comprising:

[0035] 1. Preparation of amine salt:

[0036] 1. Put the process amount of toluene (2362.5L) into the reaction kettle according to the feeding ratio, add about 50L hydrochloric acid solution (14-18%), stir for more than 10 minutes, let stand for more than 10 minutes, and separate the hydrochloric acid layer; then add about 200L drinking water, stir for more than 10 minutes, let stand for more than 10 minutes, and separate the water layer.

[0037] 2. Put in 315kg of ibuprofen and 204.75kg of octylglucamine according to the ratio, seal the hole cover, stir and heat up to 76-80°C, and keep it warm for more than 0.5 hours.

[0038] 3. Transfer the material to an amine salt crystallization kettle, add about 3.15L of purified water, and then cool down to crystallize. After the temperature drops to 18-22°C, put the material in a centrifuge to dry (10-15min), and then wash it with toluene 1 time (30~50L), rinse ...

Embodiment 3

[0051] A preparation method of Dexibuprofen, said method comprising:

[0052] 1. Preparation of amine salt:

[0053] 1. Put the process amount of toluene (2520L) into the reaction kettle according to the feeding ratio, add about 50L hydrochloric acid solution (14-18%), stir for more than 10 minutes, let stand for more than 10 minutes, separate the hydrochloric acid layer; then add about 200L For drinking water, stir for more than 10 minutes, let it stand for more than 10 minutes, and separate the water layer.

[0054] 2. Put in 315kg of ibuprofen and 236.25kg of octylglucamine according to the ratio, seal the hole cover, stir and heat up to 76-80°C, and keep it warm for more than 0.5 hours.

[0055] 3. Transfer the material to the amine salt crystallization kettle, add about 6.3L of purified water, and then cool down to crystallize. After the temperature drops to 18-22°C, put the material in a centrifuge to dry (10-15min), and then wash it with toluene 1 time (30~50L), rinse...

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Abstract

The invention discloses a preparation method of dexibuprofen. The method comprises the following steps: (1) adding toluene into a reaction kettle, adding ibuprofen and N-n-octyl-D-glucamine, heating to 76-80 DEG C, keeping the temperature to react for more than 0.5 hour, transferring the material into an amine salt crystallization kettle, adding purified water, cooling to crystallize, cooling to 18-22 DEG C, performing centrifugal separation, washing a product and drying to obtain a dexibuprofen salt of the N-n-octyl-D-glucamine, with the feeding ratio of the ibuprofen, the N-n-octyl-D-glucamine, the toluene and the purified water is 1:(0.65-0.75):(7.5-8):(0.01-0.02); (2) carrying out a hydrolysis reaction to separate out the N-n-octyl-D-glucamine; and (3) carrying out an acidification reaction to separate out the dexibuprofen. The applicant finally determines that the ratio of the volume of the added purified water to the weight of the ibuprofen is (0.01-0.02) L: 1kg when the amine salt is prepared, so that the melting point of the dexibuprofen reaches the qualified standard of 135-140 DEG C while the molar yield of the dexibuprofen is high.

Description

technical field [0001] The invention relates to the technical field of organic synthesis, in particular to a preparation method of Dexibuprofen. Background technique [0002] The process of separating the racemate into pure left-handed body or pure right-handed body is called the resolution of racemate, and chemical resolution is one of the common separation methods. The chemical method uses a resolving agent to resolve the racemate, and the resolving agent used is usually an optically active organic acid-base. Dexibuprofen is the dextrorotatory form of ibuprofen. Studies have found that the pharmacological activity of ibuprofen mainly comes from the dextro-isomer, which has higher curative effect compared with the racemate of ibuprofen at the same dose, and the therapeutic effect can be achieved with a smaller dose. Dexibuprofen and ibuprofen have the same effect and use, but the doses of 150mg and 300mg of the former are equivalent to the efficacy of the latter 200mg and...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C51/41C07C51/02C07C51/43C07C57/30C07C213/08C07C215/10
CPCC07C57/30C07C51/487C07B57/00C07C51/412C07C51/02C07C51/43C07C213/08C07B2200/07C07C215/10
Inventor 赵平刘新程志刚梁群杨宜平杨寿松孔虎林官倩倩成森周勇廖敏杰李宁张雪芹刘玲杨慈海
Owner HUBEI BIOCAUSE HEILEN PHARM CO LTD
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