Parecoxib preparation method

A technology of parecoxib and valdecoxib, which is applied in the direction of organic chemistry, can solve the problems of expensive reagents, high equipment requirements, and long reaction time, and achieve simple and feasible process, low equipment requirements, and low raw material low cost effect

Inactive Publication Date: 2013-06-26
深圳市资福药业有限公司
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  • Claims
  • Application Information

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Problems solved by technology

[0007] Its main disadvantages are: butyllithium has high chemical reactivity and high safety requirements for the reaction, which is not conducive to industrial production, and fluoride is more serious to the environment, which increases the difficulty of three wastes treatment
[0010] The main disadvantage of this method is: the reaction requires the use of more expensive reagents, such as chloroacetylation requires the use of expensive 2,6-lutidine as an acidic agent, and the reaction time is relatively long, requiring 24 hours, the reaction system It is acidic, requires high equipment, and increases production

Method used

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Examples

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Embodiment 1

[0040] 1. Preparation of Benzophenone Oxime

[0041] Add 200 g of 1,2-benzophenone (purchased from Tianjin Guangfu Fine Chemical Research Institute), 92.2 g of hydroxylamine hydrochloride (1.3 mol) (purchased from Tianjin Guangfu Fine Chemical Research Institute) and 400 ml of ethanol into the reaction bottle, and add 134 g of Ethylamine (1.3mol) (purchased from Tianjin Guangfu Fine Chemical Research Institute), heated up to 70-75°C and kept stirring for 4 hours, then cooled to 50-60°C, distilled under reduced pressure to remove ethanol to obtain an oily substance, added 500ml of water, oily After solidification, stir vigorously for 30 minutes to disperse, filter, wash with water (300ml×1), and wash with solvent (water:ethanol=2:1, 300ml×2). Dry at 50°C for 4-6 hours to obtain 194 g of white solid, yield 90%.

[0042] 2. Preparation of 4,5-dihydro-5-methyl-5-hydroxy-3,4-diphenylisoxazole

[0043] Under the protection of nitrogen, add 120g of benzophenone oxime and 500ml of t...

Embodiment 2

[0050] The preparation method of Example 2 is similar to that of Example 1, except that there is no preparation step of benzophenone oxime, and the commercially available benzophenone oxime (purchased from Tianjin Madsen Pharmaceutical Technology Co., Ltd.) is directly used for subsequent preparation. Valdecoxib as a white powder solid and parecoxib as a white solid were also obtained.

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Abstract

A parecoxib preparation method comprises the following steps: reacting diacetophenone oxime with ethyl acetate in a lithium diisopropylamide/tetrahydrofuran system to generate 4,5-dihydro-5-methyl-5-hydroxy-3,4-dibenzylisoxzzole; reacting 4,5-dihydro-5-methyl-5-hydroxy-3,4-dibenzylisoxzzole with halogenated sulfonic acid, and ammonolyzing to obtain valdecoxib; and reacting valdecoxib with propionic anhydride to obtain parecoxib. Compared with the prior art, the preparation method disclosed in the invention has the advantages of low initial raw material cost, simple and feasible technological process, low equipment requirement, and suitableness for the industrialized large-scale production.

Description

technical field [0001] The present application relates to a method for preparing parecoxib. Background technique [0002] Parecoxib is a specific inhibitor of cyclooxygenase-2 (COX-2), a prodrug of valdecoxib, and belongs to the coxib analgesics in anti-arthritis drugs. Parecoxib is used for the short-term treatment of pain after surgery. The sodium salt of parecoxib is clinically used as an injection. [0003] At present, the preparation methods of parecoxib can be divided into the following two categories according to the different starting materials: the preparation method using 1,2-benzophenone as the starting material and the method using 1-phenylacetone as the starting material method of preparation. [0004] Wherein, there are three kinds of preparation methods using 1,2-benzophenone as the starting material: [0005] Method 1: (WO2003029230) using 1,2-benzophenone as the starting material, reacting with hydroxylamine hydrochloride to form benzophenone oxime, cond...

Claims

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Application Information

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IPC IPC(8): C07D261/08
Inventor 郝宏山
Owner 深圳市资福药业有限公司
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