Method for preparing 2, 4, 5-trifluoro-phenylacetic-acid

Abstract

The invention provides a method for preparing 2, 4, 5-trifluoro-phenylacetic-acid. The method adopts 1, 2, 4-trifluoro-benzene to react with polyformaldehyde and chlorinating agent to obtain 2, 4, 5-trifluoro-benzyl chloride, and adopts the 2, 4, 5-trifluoro-benzyl chloride to react with cyaniding agent in ionic liquid to obtain 2, 4, 5-trifluoro-benzyl cyanide, and then the 2, 4, 5-trifluoro-benzyl cyanide is hydrolyzed in acid or alkalic conditions to obtain the 2, 4, 5-trifluoro-phenylacetic-acid. The preparation method for preparing 2, 4, 5-trifluoro-phenylacetic-acid requires cheap and available materials, and has moderate reaction conditions, less three-wastes and better safety; industrialized production can be easily realized, the product purity is high, and quality is stable, thuscompletely meeting the using requirement of 2, 4, 5-trifluoro-phenylacetic-acid as a pharmaceutical intermediate.

Description

technical field [0001] The invention relates to the technical field of preparation methods of 2,4,5-trifluorophenylacetic acid. Background technique [0002] 2,4,5-Trifluorophenylacetic acid is a key intermediate in the synthesis of Sitagliptinphosphate / Januvia (trade name), a drug for treating type II diabetes. US Patent No. 068,141 reported that 2,4,5-trifluorobromobenzene and diethyl malonate were reacted under basic conditions to obtain 2,4,5-trifluorophenylacetic acid after hydrolysis. This route requires high reaction conditions, poor atom economy, and is not suitable for industrial production. U.S. Patent No. 6,870,067 reported that 2,4,5-trifluorobromobenzene was made into Grignard reagent, reacted with allyl bromide, and then oxidized with periodic acid under the catalysis of ruthenium trichloride to obtain 2,4,5 - Trifluorophenylacetic acid. The Grignard reaction in this method often adopts low-boiling-point volatile solvents such as ether, which are prone to ex...

AI Technical Summary

Problems solved by technology

In this route, chlorosulfonic acid has a very strong pungent smell, poor safety, and the phase transfer catalyst is difficult to recycle, the atom economy is poor, the production cost is greatly increased, and the environmental friendliness is poor, so it is not suitable for industrialized production

Chinese patent 200810187895.9 reports that trifluorobenzyl halides are used to make Grignard reagents, and then react with carbon dioxide to obtain 2,4,5-trifluorophenylacetic acid. This method requires high anhydrous conditions, difficult operation, poor safety, and is not suitable for industrialization.

[0003] 2,4,5-Trifluorophenylacetonitrile needs to be hydrolyzed after separation and purification, and the separation and purification of products has always been a difficult problem in synthetic chemistry. Extraction and separation with water is only suitable for hydrophilic products, and distillation technology is not suitable for low-volatility products. products, the use of organic solvents can cause cross-contamination

With the improvement of people's awareness of environmental protection, the voice of green chemistry is getting higher and higher all over the world, and the traditional solvent extraction technology needs to be improved urgently.

Images