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A technology of flunixin meglumine and flunixin, which is applied in the field of preparation of flunixin meglumine, can solve the problems of high difficulty in recovery, purification and utilization, and increased production costs, and achieve low cost and short reaction time , the effect of high yield
Active Publication Date: 2019-01-15
龙岩台迈三略制药有限公司 +1
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Problems solved by technology
However, the main raw material of this patent is 2-methyl-3-trifluoromethylaniline, and it is more difficult to recover, purify and utilize it when using twice the amount of feed, which will inevitably lead to an increase in the entire production cost.
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Embodiment 1
[0024] The preparation method of flunixin meglumine in the present embodiment comprises the following steps:
[0025] (1) Add 2-chloronicotinic acid and 2-methyl-3-trifluoromethylaniline into aqueous sodium hydroxide solution and stir, and the 2-chloronicotinic acid and 2-methyl-3-trifluoromethylaniline The molar ratio of aniline is 3:1; the molar ratio of the 2-chloronicotinic acid to the sodium hydroxide used to prepare the aqueous sodium hydroxide solution is 1:2; add ethylene glycol and chain polyethylene glycol dialkyl Ether and catalyst A, the consumption of described chain polyethylene glycol dialkyl ether is 3% of the feeding quality of 2-chloronicotinic acid; Described catalyst A is p-toluenesulfonic acid and copper oxide, and described p-toluenesulfonic acid The molar ratio of toluenesulfonic acid to copper oxide is 3:1; control the temperature at 45°C, adjust the pH of the solution after reacting for 0.6 hours, leave to separate after stirring, filter after stirring...
Embodiment 2
[0028] The difference from Example 1 is that the phase transfer catalyst in the step (1) is benzyltriethylamine chloride.
Embodiment 3
[0030] The difference with embodiment 1 is: the phase transfer catalyst in the described step (1) is tetrabutylammonium bisulfate.
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Abstract
The invention discloses a preparation method of flunixin meglumine the preparation method, and the method specifically comprises the following steps: (1) adding 2-chloronicotinic acid and 2-methyl-3-trifluoromethyl aniline into a sodium hydroxide water solution for stirring, adding ethylene glycol as well as a phase transfer catalyst and p-toluenesulfonic acid and copper oxide, controlling the temperature and time, adjusting the pH value of the solution, stirring, standing, layering, stirring, filtering, washing filter cake, and drying to obtain flunixin; and (2) reacting the flunixin obtainedin the step (1) with N-methylglucosamine in isopropyl alcohol, and meanwhile, adding a filler; carrying out heating reflux, filtering, cooling, stirring and crystallizing, carrying out crystal suction filtration, and washing crystals with isopropanol to obtain the flunixin meglumine. The preparation method of the flunixin meglumine is convenient and simple in operation, the reflecting efficiencyis high, the reaction temperature is low, the reaction time is short, and the cost is low; moreover, the prepared flunixin meglumine is high in purity and high in yield.
Description
technical field [0001] The invention belongs to the field of veterinary drug synthesis, and in particular relates to a preparation method of flunixin meglumine. Background technique [0002] Flunixin meglumine is a new type of non-steroidal animal-specific antipyretic and analgesic drug, which belongs to the derivative of nicotinic acid and is a cyclooxygenase inhibitor. Developed by Schering-Plough in the 1990s, it has been widely used in the United States, France, Switzerland, Germany, the United Kingdom and many other countries. At present, the Ministry of Agriculture of my country has approved some veterinary drug factories to produce flunixin meglumine. In veterinary clinical practice, the drug is used in horses to relieve inflammation and pain caused by muscle abnormalities, relieve horses' visceral colic, and treat foals' diarrhea, tremors, colitis, etc.; it is used in cattle to treat respiratory diseases, endotoxin-induced mastitis; for dogs to treat arthritis, fev...
Claims
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