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Synthesis method of celecoxib

A synthesis method and a condensation reaction technology are applied in the field of preparation of celecoxib, which can solve the problems of affecting product quality and yield, low celecoxib yield and the like, and achieve a sufficient reaction, improved competitiveness and less impurities. Effect

Inactive Publication Date: 2012-03-28
JIANGXI SYNERGY PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The yield of this process celecoxib is low, only 46%; The main reason is that using sodium methylate as a catalyst fails to react completely, and the diketone without separation contains p-methylacetophenone, which is combined with p-sulfonamide group The reaction of phenylhydrazine hydrochloride produces new impurities which affect the quality and yield of products

Method used

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  • Synthesis method of celecoxib

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Embodiment 1

[0023] Preparation of 1-(4-methylphenyl)-4,4,4-trifluoro-1,3-butanedione

[0024] Put 400ml of toluene and 25g of sodium hydride into a 1000ml four-necked bottle successively, stir, raise the temperature to 60~65°C, add 40g of p-methylacetophenone dropwise, and simultaneously add 50g of ethyl trifluoroacetate dropwise. After dropping, keep warm at 60-65°C for 1 hour, cool to 30°C, add 120ml of 15% hydrochloric acid dropwise, let stand and separate after dropping, and evaporate the organic layer to dryness under reduced pressure to obtain the residue 1-(4-methyl 65.9 g of phenyl)-4,4,4-trifluoro-1,3-butanedione, yield 96%.

Embodiment 2

[0026] Preparation of 1-(4-methylphenyl)-4,4,4-trifluoro-1,3-butanedione

[0027] Put 400ml of toluene and 25g of sodium hydrogen into a 1000ml four-necked bottle successively, stir, control the temperature to 20~25°C, add 40g of p-methylacetophenone dropwise, and simultaneously add 50g of ethyl trifluoroacetate dropwise. After dripping, keep it warm at 40-45°C for 5 hours, cool to 30°C, add 120ml of 15% hydrochloric acid dropwise, let stand to separate after dripping, evaporate the organic layer to dryness under reduced pressure, and add 200ml of petroleum ether to the residue to crystallize 1- (4-methylphenyl)-4,4,4-trifluoro-1,3-butanedione 62.3g, yield 91%.

Embodiment 3

[0029] Preparation of 1-(4-methylphenyl)-4,4,4-trifluoro-1,3-butanedione

[0030] Put 400ml of toluene and 40g of potassium hydride into a 1000ml four-neck bottle successively, stir, control the temperature to 5~10°C, add 40g of p-methylacetophenone dropwise, and simultaneously add 50g of ethyl trifluoroacetate dropwise. After dropping, keep warm at 30-35°C for 6 hours, cool to 30°C, add 120ml of 15% hydrochloric acid dropwise, let stand and separate after dropping, evaporate the organic layer to dryness under reduced pressure, and add 200ml of petroleum ether to the residue to crystallize 1- (4-methylphenyl)-4,4,4-trifluoro-1,3-butanedione 59g, yield 86%.

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Abstract

The invention relates to a synthesis method of celecoxib, which comprises the following specific steps of: 1, carrying out claisen condensation on p-methylacetophenone and trifluoroacetic acid ethyl esters in an aprotic organic solvent under the catalysis of alkali to obtain 1-(4-methylphenyl)-4,4,4-trifluoro-1,3-butanedione; and 2, reacting the obtained 1-(4-methylphenyl)-4,4,4-trifluoro-1,3-butanedione with sulfonamide-phenylhydrazine hydrochloride to obtain celecoxib, wherein in the step 1, the alkali for catalysis is selected from one or more of sodium hydride, potassium hydride, lithium hydride and calcium hydride. The synthesis method of celecoxib provided by the invention is easy to operate, high in yield, high in product purity and easy for industrial production.

Description

technical field [0001] The present invention relates to the field of organic chemistry, in particular to a preparation method of Celecoxib. Background technique [0002] Celecoxib, molecular formula: C 17 h 14 f 3 N 3 o 2 S, with a molecular weight of 381, is a compound of chemical formula (1), and its chemical name is: 4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl] Benzenesulfonamide (CAS Registry No. 169590-42-5). Celecoxib is a highly selective COX-2 inhibitor. It is a new type of antipyretic, analgesic and anti-inflammatory drug with high efficiency and low toxicity. It is used for the treatment of rheumatoid arthritis, osteoarthritis and other inflammatory pains. Since it was launched on the market, the drug has shown the advantages of definite curative effect, mild and few adverse reactions. [0003] The preparation method of celecoxib was first disclosed by (WO95 / 15316) as follows: [0004] [0005] 1 [0006] The process is to obtain 1-(4-methylp...

Claims

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Application Information

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IPC IPC(8): C07D231/12
Inventor 蒋慧纲蒋元森徐烘材
Owner JIANGXI SYNERGY PHARMA
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