A kind of synthetic method of cox-2 enzyme inhibitor celecoxib intermediate

A technology of COX-2 and celecoxib, applied in chemical instruments and methods, condensation preparation of carbonyl compounds, preparation of carbon-based compounds, etc., can solve environmental problems of industrial wastewater, strong alkalinity of sodium methoxide, easy hydrolysis and other problems, Achieve broad market prospects and economic benefits, simple operation, and low pollution

Active Publication Date: 2016-04-27
HEBEI UNIVERSITY OF SCIENCE AND TECHNOLOGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Because sodium methoxide is too alkaline and easily hydrolyzed, it is extremely inconvenient in practical application
What is more serious is that after the reaction is completed, water is required to quench and wash away the chemical substances introduced by sodium methoxide, thereby producing industrial waste water and causing environmental problems

Method used

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  • A kind of synthetic method of cox-2 enzyme inhibitor celecoxib intermediate
  • A kind of synthetic method of cox-2 enzyme inhibitor celecoxib intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Add 200mL of ethanol, 200mmol (26.8mL) of p-methylacetophenone (I), 600mmol (72mL) of ethyl trifluoroacetate (II), 360mmol of anhydrous potassium carbonate in a 500mL single-port bottle, and react at -20°C 28h. Potassium carbonate and potassium bicarbonate were recovered by suction filtration. The mother liquor is rectified to recover the solvent and unreacted raw materials. Add an equal volume of water to the rectification raffinate, adjust the pH value to 6 with 10% hydrochloric acid, extract 4 times with petroleum ether, 70 mL each time, combine the organic phases, concentrate, and freeze-dry to obtain 44.3 g of light yellow solid product (III) , the yield was 96.3%.

Embodiment 2

[0028] Add 200mL of acetonitrile-isopropanol (1:1), 200mmol (26.8mL) of p-methylacetophenone (I), 600mmol (72mL) of ethyl trifluoroacetate (II), and 360mmol of Potassium carbonate with a diameter of 600nm was reacted at 40°C for 24h. Potassium carbonate and potassium bicarbonate are recovered by suction filtration, and can be reused after high temperature treatment. The mother liquor is rectified to recover the solvent and unreacted raw materials for the next reaction. Add an equal volume of water to the rectification raffinate, adjust the pH value to 6 with 10% hydrochloric acid, extract 4 times with ethyl acetate, 70 mL each time, combine the organic phases, concentrate and lyophilize to obtain a light yellow solid product (III) 45.6 g, the yield is 99.08%.

Embodiment 3

[0030] Add 200mL of ethylene glycol dimethyl ether, 200mmol (26.8mL) of p-methylacetophenone (I), 600mmol (72mL) of ethyl trifluoroacetate (II), and 360mmol of carbonic acid with a particle size of 200nm in a 500mL single-port bottle. Potassium, reflux reaction for 16h. Potassium carbonate and potassium bicarbonate are recovered by suction filtration, and can be reused after high temperature treatment. The mother liquor is rectified to recover the solvent and unreacted raw materials for the next reaction. Add an equal volume of water to the rectification raffinate, adjust the pH value to 6 with 10% hydrochloric acid, extract 4 times with diethyl ether, 70 mL each time, combine the organic phases, concentrate, and lyophilize to obtain 44.8 g of a pale yellow solid product (III). The yield was 97.4%.

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Abstract

The invention belongs to the technical field of clean synthesis and particularly relates to a synthetic method of a COX-2 enzyme inhibitor celecoxib intermediate. The method comprises the following steps: reacting initial raw materials (ethyl trifluoroacetate (II) and p-methylacetophenone (I)) in the presence of carbonate serving as alkali in an organic solvent and obtaining the celecoxib intermediate 4,4,4-trifluoro-(4-methylphenyl)-1,3-butanedione (III) with the yield of 83%-99%. In the whole process, the raw material consumption is low, alkali and a solvent can be recycled, and the generation of three wastes is low; and the method has good industrial prospect.

Description

technical field [0001] The invention belongs to the technical field of clean synthesis, in particular to a method for synthesizing a COX-2 enzyme inhibitor celecoxib intermediate, more specifically a COX-2 enzyme inhibitor celecoxib intermediate 4,4,4 - Synthesis of trifluoro-(4-methylphenyl)-1,3-butanedione (III). Background technique [0002] Non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely used prescription drugs in the world, with more than 30 million people taking them every day. They are drugs with antipyretic, analgesic, anti-inflammatory and anti-rheumatic effects. The main mechanism of its action is to inhibit the cyclooxygenase (COX) in the body and reduce the synthesis of prostaglandins that cause fever, swelling and pain sensitization. NSAIDs fall into two categories, nonselective NSAIDs and selective COX-2 inhibitors. Non-selective NSAIDs, also known as traditional NSAIDs (such as ibuprofen, diclofenac, meloxicam, etc.), have inhibitory effec...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C45/48C07C49/80
CPCC07C45/455C07D231/12C07C49/80
Inventor 刘守信王经坤冯娟李军章
Owner HEBEI UNIVERSITY OF SCIENCE AND TECHNOLOGY
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