Synthesis method of mefenamic acid

A synthetic method, mefenamic acid technology, applied in chemical instruments and methods, preparation of organic compounds, organic chemistry, etc., can solve problems such as waste of raw materials, low operation safety, environmental pollution, etc., and reduce production costs and process steps The effect of simplicity and high operational safety

Active Publication Date: 2010-05-12
NINGBO SMART PHARMA
View PDF0 Cites 15 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Used alkali in this method is sodium acetate, and catalyzer is copper acetate, and price is all more expensive, so production cost is high
And main reactant 2, the molar number of 3-xylaniline is twice of o-chlorobenzoic acid, the raw material waste is serious, and also do not mention the purification method of crude product in this synthetic method, target product purity is low, not necessary Suitable for industrial production
[0004] There are also reports in the literature of preparing mefenamic acid, using dimethyl sulfoxide, sulfolane, N, N-dimethylformamide, and organic solvents such as benzene, toluene, xylene, trimethylbenzene, and using quaternary ammonium salts Phase transfer catalysts not only increase the production cost, but the use of the above-mentioned organic solvents causes great pollution to the environment, and also causes certain harm to the operators. The operation safety is low and the environment is not friendly

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Synthesis method of mefenamic acid
  • Synthesis method of mefenamic acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Add 500kg of o-chlorobenzoic acid, 500kg of 2,3-dimethylaniline, 350kg of sodium carbonate, 25kg of anhydrous copper sulfate and 1500kg of water in the reaction vessel, stir evenly, and heat to 100~110°C, React for 15 hours under constant stirring; then dilute the above reaction mixture with water, acidify with dilute hydrochloric acid to PH = 2-3, cool to room temperature after acidification, then filter, and wash the filter residue with warm water at a temperature of 35-40°C to obtain 720kg of formazan An acid crude product.

[0024] Add 720kg of crude mefenamic acid to the reaction vessel, then add 800kg of dimethylformamide to reflux for 3 hours, then cool the solution to room temperature, precipitate solids, then filter, collect the filtered solids into a clean container, and filter to obtain The solid was redissolved in dimethylformamide, heated to reflux for 3 hours, and then cooled to room temperature. A light yellow to white high-purity final product, mefenamic...

Embodiment 2

[0028] Add 500kg of o-chlorobenzoic acid, 400Kg of 2,3-dimethylaniline, 350kg of sodium carbonate, 25kg of anhydrous copper sulfate and 1500kg of water into the reaction vessel, mix well, heat to 90-120°C, and continue The reaction was stirred for 20h. Then the above reaction mixture was diluted with water, acidified with dilute hydrochloric acid to pH=2-3, the acidified reaction solution was cooled to room temperature, then filtered, and the filter residue was washed with warm water to obtain 620 kg of crude mefenamic acid.

[0029] Add 620kg of crude mefenamic acid to the reaction vessel, then add 700kg of acetic acid, stir and react at room temperature for 1 hour, filter and collect a light brown solid, then dissolve the light brown solid in 600kg of dimethylformamide, and heat to reflux After cooling to room temperature for 1 hour, a light yellow to white final product with high purity was precipitated, and dried to constant weight to obtain 490 kg of the final product mef...

Embodiment 3

[0033] Investigate the impact of different feeding ratios of 2,3-dimethylaniline and o-chlorobenzoic acid on the yield of the target product, the results are shown in Table 1:

[0034] Table 1

[0035] label

[0036] Reaction conditions are: sodium carbonate 0.33mol, copper sulfate 0.01mol and water 150g, reaction temperature 90~120 ℃, other reaction conditions are the same as embodiment 1. The results show that when the weight ratio of 2,3-dimethylaniline to o-chlorobenzoic acid is 1:1, that is, when the molar ratio is 1.3:1, the yield of the target product is ideal.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
melting pointaaaaaaaaaa
Login to view more

Abstract

The invention discloses a synthesis method of mefenamic acid. The method comprises the following steps: firstly adding o-halophenylacetic acid, 2,3-dimethylaniline, acid binding agent, catalyst and water in a reaction container to react; then adding water in the reaction mixture to dilute, then acidifying to ensure that the pH value is 2-3, cooling to the room temperature, filtrating, washing filter residue with warm water to obtain raw mefenamic acid; then adding the raw mefenamic acid in a reaction container, then adding organic solvent to perform recrystallization, filtrating to obtain solid, dissolving the obtained solid in organic solvent to perform second recrystallization, filtrating, and drying to obtain the target product. The synthesis method of mefenamic acid in the invention has the advantage that the production cost is low, the utilization of reaction raw materials is complete, the product purity is high, the environmental pollution is little, the operation safety is high, and the method is environmentally friendly and is applicable to industrial production.

Description

technical field [0001] The invention relates to a synthetic method of mefenamic acid. Background technique [0002] Mefenamic acid (2-[(2,3-dimethylphenyl)amino]benzoic acid) is a non-steroidal anti-inflammatory drug, commonly used to relieve short-term moderate pain, such as muscle pain, headache, toothache, etc. ( H.G. Brittain, "Analytical profiles of Drug substances and Excipients," PP 179-211, Academic Press, New York, 2002). In addition, mefenamic acid is also a precursor for the synthesis of acridine antimalarials and anticancer drugs (S. Girault, P. Grellier, A. Bercibar and L. Maes, J. Med. Chem., 43, 2646-2654). [0003] Girisha et al. (H.R.Girisha et. al. Journal of Chemical Research, 2006, 342-344) introduced a method for synthesizing mefenamic acid. The alkali used in the method is sodium acetate, and the catalyzer is copper acetate, and the price is all expensive, so the production cost is high. And main reactant 2, the molar number of 3-xylaniline is twice ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C07C229/58C07C227/08
Inventor 库拉利
Owner NINGBO SMART PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap