Method for preparing travoprost intermediate

Abstract

The invention relates to a method for preparing a travoprost intermediate, which is prepared by performing a reaction of dimethyl methyl phosphonate, (3-trifluoromethyl phenoxyl) ethyl acetate and lithium diisopropylamide in an organic solvent. The method for preparing the travoprost intermediate has the advantages of simple process, mild reaction conditions, high yield and suitability for industrialized production.

Description

technical field

[0001] The invention belongs to the field of drug synthesis, and in particular relates to a preparation method of a travoprost intermediate. Background technique

[0002] Travoprost (Travoprost) is a PG drug approved by the US FDA in September 2006 for the treatment of primary open-angle glaucoma and ocular hypertension. 3-(3-trifluoromethylphenoxy)-2-oxopropyl phosphate dimethyl ester is a key intermediate for the preparation of travoprost.

[0003] In the prior art, US3953435 discloses a method for preparing 3-(3-trifluoromethylphenoxy)-2-oxopropyl dimethyl phosphate, (3-trifluoromethylphenoxy)acetic acid Ethyl ester was reacted with dimethyl methyl phosphate in tetrahydrofuran / n-butyl lithium / n-hexane, and the yield was 67%. The reaction conditions of this method are harsh, and the reaction temperature is required to be between -60 and -55°C. After-treatment, high-vacuum fractional distillation must be carried out first, and then purified by silica gel c...

Images