Synthetic method for 2-methyl-3-trifluoromethyl phenylamine

Abstract

The invention discloses a synthetic method for 2-methyl-3-trifluoromethyl phenylamine. The method comprises the following steps: 1) preparing 3-nitro-4-methyl benzenesulfonic acid; 2) preparing 3-nitro-4-methyl-5-bromobenzenesulfonic acid; 3) preparing 2-nitro-6-bromotoluene; 4) preparing 2-nitro-6-trichloromethyl toluene; 5) preparing 2-nitro-6-trifluoromethyl toluene; 6) preparing 2-methyl-3-trifluoromethyl phenylamine, that is, adding 5% palladium-charcoal and methanol in 2-nitro-6-trifluoromethyl toluene obtained in step 5), carrying out hydrogenation reduction at a temperature of 35 DEG C and removing a catalyst so as to obtain 2-methyl-3-trifluoromethyl phenylamine. According to the invention, p-toluenesulfonic acid is used as a starting material, and therefore, disadvantages of theprior art are overcome and yield of a target product is improved.

Description

technical field [0001] The invention relates to poultry medicine, which is a method for synthesizing the intermediate 2-methyl-3-trifluoromethylaniline of special medicine for animals. Background technique [0002] 2-Methyl-3-trifluoromethylaniline is an intermediate of flunixin meglumine, which is one of the few approved non-steroidal drugs for animals, mainly through the inhibition of epoxy It reduces the production of inflammatory mediators such as prostaglandins and exerts antipyretic, anti-inflammatory and analgesic effects. The synthetic routes of the drug all adopt 2-methyl-3-trifluoromethylaniline as an intermediate and 2-chloronicotinic acid or ethyl 2-chloronicotinic acid to undergo nucleophilic substitution on the pyridine ring to obtain flunixin, and then Flunixin and meglumine undergo an acid-base salification reaction to obtain flunixin meglumine. Due to the unique position of the substituents on the benzene ring of 2-methyl-3-trifluoromethylaniline, the syn...

AI Technical Summary

Problems solved by technology

Due to the unique position of the substituents on the benzene ring of 2-methyl-3-trifluoromethylaniline, the synthesis process is more complicated and the production cost is higher, so 2-methyl-3-trifluoromethylaniline becomes a restricted fluorine Main Factors of Nisin Meglumine Production Cost

And U.S. Patent No. 4,172,095 discloses a method for synthesizing 2-methyl-trifluoromethylaniline: take 3-trifluoromethylaniline as raw material, first condense with dimethyl sulfoxide, then rearrange, and reduce to obtain 2 -Methyl-3-trifluoromethylaniline, the main disadvantage of this method is that there is no position selectivity during the rearrangement, and two mixtures are generated, and the difference in amount is not large, which requires rectification and purification, and the yield is particularly low

The shortcoming of another U.S. patent US4831193 disclosed method is: used in the reaction more expensive trimethyl sulfoxide bromide, and n-butyllithium consumption is big, and yield is low, and cost is high

In addition, there are still methods abroad, there is no commercial starting material, the amount of n-butyl lithium is also large, the cost is high, and the yield is low. The yield of these methods ranges from 28% to 50%.