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Refining method of rebamipide

A technology of rebamipide and its refining method, which is applied in the field of preparation of high-purity rebamipide, can solve problems such as difficulty in obtaining high-purity rebamipide and residual impurities, and achieve beautiful color, simple operation and high purity Effect

Active Publication Date: 2011-09-07
JIANGXI SYNERGY PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] Although rebamipide is refined by methods such as recrystallization or pH adjustment recrystallization, there are still some impurities remaining, and it is difficult to obtain high-purity rebamipide

Method used

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  • Refining method of rebamipide

Examples

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Effect test

Embodiment 1

[0033] 1) Preparation of crude rebamipide potassium salt

[0034] Put 370ml of methanol, 37g (0.10mol) of crude rebamipide, and 8.4g of potassium hydroxide into a 1000ml four-necked bottle in sequence, stir, and raise the temperature to 60~65°C to dissolve the solid. Add 2g of activated carbon, decolorize at this temperature for 1 hour, filter, and cool the filtrate to 0°C to crystallize. Filter, and dry the filter cake under reduced pressure at 60° C. for 8 hours to obtain 32 g of crude rebamipide potassium salt;

[0035] 2) Refined rebamipide potassium salt

[0036] Put 450ml of isopropanol and 32g of crude rebamipide potassium salt into a 500ml four-neck bottle, and heat up to 65°C to dissolve the solid. Add 2 g of activated carbon, reflux for decolorization for 1 hour, filter, and cool the filtrate to 0°C for crystallization. Filter, and dry the filter cake under reduced pressure at 60°C to obtain 29 g of refined rebamipide potassium salt;

[0037] 3) High-purity rebam...

Embodiment 2

[0040] 1) Preparation of crude product of rebamipide sodium salt

[0041] Put 550ml of methanol, 37g (0.10mol) of crude rebamipide, and 4.5g (0.143mol) of sodium hydroxide into a 1000ml four-necked bottle in sequence, stir, and raise the temperature to 75-80°C to dissolve the solid. Add 2g of activated carbon, decolorize at this temperature for 1 hour, filter, and cool the filtrate to 0°C to crystallize. Filter, and dry the filter cake under reduced pressure at 60°C to obtain 30 g of crude rebamipide sodium salt;

[0042] 2) Refined rebamipide sodium salt

[0043] Put 240ml of isopropanol, 120ml of ethyl acetate, and 30g of crude rebamipide sodium salt into a 500ml four-necked bottle, and raise the temperature to 75~80°C to dissolve the solid. Add 2 g of activated carbon, reflux for decolorization for 1 hour, filter, and cool the filtrate to 0°C for crystallization. Filter and dry the filter cake under reduced pressure at 60°C to obtain 27g of refined rebamipide sodium salt...

Embodiment 3

[0064] 1) Preparation of the crude product of rebamipide potassium salt

[0065] Put 300ml of isopropanol, 37g (0.10mol) of crude rebamipide, 13g of potassium carbonate and 60ml of water into a 1000ml four-necked bottle in turn, stir, and raise the temperature to 75~80°C to dissolve the solid. Add 2 g of activated carbon, decolorize at this temperature for 1 hour, filter, and cool the filtrate to 0 °C to crystallize 8. Filter, and dry the filter cake under reduced pressure at 60° C. to obtain 28 g of crude rebamipide potassium salt;

[0066] 2) Refined rebamipide potassium salt

[0067] Put 350ml of isopropanol and 28g of crude rebamipide potassium salt into a 500ml four-neck bottle, and raise the temperature to 75~80°C to dissolve the solid. Add 2 g of activated carbon for decolorization for 1 hour, filter, cool the filtrate to 0°C, crystallize, filter, and dry the filter cake under reduced pressure at 60°C to obtain 26 g of refined rebamipide potassium salt;

[0068] 3) H...

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Abstract

The invention discloses a refining method of rebamipide, comprising the following steps of: firstly, reacting a rebamipide crude product with alkali to obtain a rebamipide salt crude product, recrystallizing to obtain a refined rebamipide salt, and acidifying to obtain refined rebamipide. In each step of operation for refining the rebamipide, active carbon can be respectively added for decoloring. Rebamipide acquired by the refining method disclosed by the invention has esthetic color of the product, good quality and high purity; and determined by HPLC (High Performance Liquid Chromatography), the purity is 99.8% and the total content of impurities is less than 0.20%. The used solvent is simple, a high boiling solvent needs not to be used, and in addition, the refining method is simple tooperate, has simple flow and equipment and is easy to realize industrial production.

Description

technical field [0001] The invention belongs to the field of organic chemistry, and specifically relates to a preparation method of high-purity rebamipide. Background technique [0002] Rebamipide, molecular formula: C19H15ClN2O4, molecular weight: 370.79, is a quinolone compound with chemical formula (1), chemical name: 2-(4-chlorobenzamido)-3-[2( 1H)-quinolon-4-yl]propanoic acid (CAS accession number 111911-87-6). It can improve gastric motility and has a significant effect on gastric mucosal damage caused by gastric ulcer, acute gastritis or acute exacerbation of chronic gastritis. [0003] [0004] The preparation method of rebamipide has been reported in many patents and literatures. The common synthetic route disclosed in Japanese patent (JP2008143794A) is as follows: [0005] [0006] In the products prepared by the above process, the content of rebamipide is generally low, and the obvious impurities are: compound (2), compound (4), compound (5) and compound (...

Claims

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Application Information

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IPC IPC(8): C07D215/227
Inventor 黄国军叶四明蒋元森徐烘材
Owner JIANGXI SYNERGY PHARMA
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