Method for preparing benzoic-2-[[1-methyl-2-[3-(trifluoromethyl)-phenyl] ethyl] amido] ethyl ester hydrochlorate

Abstract

The invention provides a method for preparing benzoxy -2-[[1-methyl-2-[3-(trifluoromethyl)-phenyl]ethyl]amino] carbethoxy hydrochloride (I), comprising the following steps that: 1-(3-fluoromethylphenyl)-2-(2-hydroxy ethyl) aminopropane (III) is prepared in one step through a condensation reaction between 3-trifluoromethyl propiophenone (IV) and ethanolamine in an organic solvent under catalysis of a p-toluenesulfonic acid, and hydrogenization under the action of catalysis of a palladium / a carbon; the 1-(3-fluoromethylphenyl)-2-(2-hydroxy ethyl) aminopropane (III) is reacted with a hydrochloric acid to generate hydrochloride (II) of the 1-(3-fluoromethylphenyl)-2-(2-hydroxy ethyl) aminopropane (III); the hydrochloride (II) is refluxed and dehydrated in the presence of an organic menstruum; esterification of the hydrochloride (II) and benzoyl chloride are carried out to generate a crude product of a compound (I); and the crude product is added with a mixed solvent for refining to prepare a finished product of the compound I. The method has the advantages of stable process, simple operation, easy control of reaction condition, less reaction steps, convenient post-processing, less three wastes, good product quality, high yield rate and low production cost, is capable of continuously and circularly using a mother liquid and is applicable to industrial production.

Description

technical field [0001] The present invention relates to a preparation process of a compound, in particular to an amphetamine-type hypoglycemic and hypolipidemic drug, benzoic acid-2-[[1-methyl-2-[3-(trifluoromethyl)-benzene A new process for the preparation of base] ethyl] amino] ethyl ester hydrochloride. Background technique [0002] Benzoic acid-2-[[1-methyl-2-[3-(trifluoromethyl)-phenyl]ethyl]amino]ethyl ester hydrochloride compound (I), has good hypoglycemic effect, can As a therapeutic drug for type II diabetes, blood sugar and blood lipid metabolism disorders, obesity, hyperuricemia, syndrome and other diseases. Chinese patent CN1126732C provides a benzoic acid-2-[[1-methyl-2-[3-(trifluoromethyl)-phenyl]ethyl]amino]ethyl ester hydrochloride compound (I). [0003] It can be prepared by condensing 3-trifluoromethylpropiophenone and ethanolamine, reducing with sodium borohydride, acidifying hydrochloric acid to form a salt, and esterifying. The reaction is as follows: ...

AI Technical Summary

Problems solved by technology

The process is complicated to operate, the crude product of the reduced product hydrochloride is not easy to dry, the drying is not thorough, the batch number is easy to be discarded, and the recrystallization yield is low

The esterification reaction is carried out in the solid phase, the reactants are not mixed uniformly, the quality of the obtained product is poor, the yield is low, each process requires high equipment, the post-treatment is complicated, there are many three wastes, the production cost is high, and it does not meet industrial production

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