A kind of preparation method of parecoxib sodium synthesis process impurity

A technology for the synthesis of parecoxib sodium and its application in the field of preparation of the process impurity ethyl 4-benzenesulfonate, which can solve the problems that there are no literature reports on the synthesis of impurities, and achieve the effect of simple operation and quality control of finished products

Active Publication Date: 2017-09-29
BENGBU BBCA MEDICINE SCI DEV
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

After searching, there is no report on the synthesis literature of this impurity

Method used

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  • A kind of preparation method of parecoxib sodium synthesis process impurity
  • A kind of preparation method of parecoxib sodium synthesis process impurity
  • A kind of preparation method of parecoxib sodium synthesis process impurity

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Embodiment 1

[0037] Example 1: A method for preparing parecoxib sodium synthesis process impurity 4-(5-methyl-3-phenyl-isoxazolyl) ethyl benzenesulfonate

[0038] Add 8.0 g of 5-methyl-3,4-diphenylisoxazole and 40 g of dichloromethane into the reaction flask, cool down to -5°C in an ice bath, start adding 32 g of chlorosulfonic acid dropwise, and control the internal temperature of the reaction solution to < 5 ℃. After the addition of chlorosulfonic acid was completed, the temperature was slowly raised to 35° C., and the reaction was kept for 10 hours. The reaction solution was monitored by TLC until the spot of the raw material 5-methyl-3,4-diphenylisoxazole disappeared (the developer was ethyl acetate:petroleum ether=1:6, v:v), and the reaction was stopped. Add 100 g of crushed ice to the reaction flask, stir for 1 h, pour into a separatory funnel and let stand to separate layers, and separate the lower aqueous phase. Add 5 g of anhydrous sodium sulfate to the upper organic phase, dry ...

Embodiment 2

[0044] Embodiment 2: A kind of synthetic method of parecoxib sodium process impurity 4-(5-methyl-3-phenyl-isoxazolyl) ethyl benzenesulfonate

[0045] Add 8.0 g of 5-methyl-3,4-diphenylisoxazole and 40 g of dichloromethane into the reaction flask, cool down to -5°C in an ice bath, start adding 40 g of chlorosulfonic acid dropwise, and control the internal temperature of the reaction solution to <5 ℃. After the addition of chlorosulfonic acid was completed, the temperature was slowly raised to 35° C., and the reaction was kept for 10 hours. The reaction solution was monitored by TLC until the spot of the raw material 5-methyl-3,4-diphenylisoxazole disappeared (the developer was ethyl acetate:petroleum ether=1:6, v:v), and the reaction was stopped. Add 100 g of crushed ice to the reaction flask, stir for 1 h, pour into a separatory funnel and let stand to separate layers, and separate the lower aqueous phase. Add 5 g of anhydrous sodium sulfate to the upper organic phase, dry i...

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Abstract

The invention provides a method for preparing impurities in the synthesis process of parecoxib sodium; the method uses 5-methyl-3,4-diphenylisoxazole as a raw material to synthesize the target product 4- Ethyl (5-methyl-3-phenyl-isoxazolyl)benzenesulfonate. The impurity is a genotoxic impurity of parecoxib sodium, and the study of the synthesis method of this impurity is beneficial to the study of the impurity profile of parecoxib sodium and the quality control of parecoxib sodium products. The structural formula of this impurity is as shown in the following formula:

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical synthesis, and in particular relates to a preparation method of ethyl 4-(5-methyl-3phenyl-isoxazolyl)benzenesulfonate, a process impurity produced during the synthesis of parecoxib sodium. Background technique [0002] The chemical name of parecoxib sodium is N-[[4-(5-methyl-3-phenyl-isoxazolyl)phenyl]sulfonyl]propanamide sodium salt, which is a selective cyclooxygenase- 2 inhibitors, mainly used for short-term treatment of pain after surgery. Because of its good water solubility, it is often used as an injection. [0003] During the synthesis of parecoxib sodium, a process impurity, ethyl 4-(5-methyl-3-phenyl-isoxazolyl)benzenesulfonate, is produced, which is a genotoxic impurity and is present in the final product Parecoxib Sodium Recoxib sodium should be strictly controlled. After searching, there is no report about the synthetic literature of this impurity. Therefore, the present in...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D261/08G01N30/88
CPCC07D261/08G01N30/88G01N2030/8872
Inventor 韦亚锋陈昀张瑾李士桥胡媛
Owner BENGBU BBCA MEDICINE SCI DEV
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