Chemical synthesis method for R-2-hydroxy-4-phenylbutanoate

Abstract

The invention discloses a chemical synthesis method for optical pure R-2-hydroxyl-4-phenyl ethyl butyrate. The chemical synthesis method comprises the following steps: in an organic solvent and in the presence of azodiformate and triphenylphosphine, S-2-hydroxyl-4-phenyl ethyl butyrate and paranitrobenzoic acid are reacted and then filtered; after the filtrate is condensed and the solvent is recycled, R-esterified intermediate is obtained by recrystallization; the intermediate is catalyzed in ethanol by potassium carbonate to be subjected to transesterification reaction and then filtered; the filtrate is neutralized by hydrochloric acid; after the solvent is recycled, the filtrate is extracted by ethylene dichloride which is then recycled by an organic phase; and the filtrate is distilled under reduced pressure to obtain the optical pure R-2-hydroxyl-4-phenyl ethyl butyrate with high yield. The synthesis method for the R-2-hydroxyl-4-phenyl ethyl butyrate has the advantages of safety, high efficiency, quick and convenient operation, high selectivity, good yield and low cost, simplicity, general use and suitability for industrialized production.

Description

technical field [0001] The invention relates to a preparation method of a pharmaceutical intermediate, in particular to a chemical synthesis method of ethyl R-2-hydroxy-4-phenylbutyrate. Background technique [0002] R-2-Hydroxy-4-phenylbutyric acid ethyl ester is synthesized from Benazepril, Enalapril, Lisinopril, Cilazapril, Peridole A key player in the treatment of hypertension and congestive heart failure drugs such as Perindopril, Quinapril, Spirapril and Ramipril sex intermediate. Due to the importance of ethyl R-2-hydroxy-4-phenylbutyrate in the synthesis of this class of drugs, its preparation has always been one of the hotspots of research at home and abroad, attracting many chemical science and technology workers to their preparation methods. Extensive research was conducted and a large number of preparation methods were reported. In summary, the methods mainly include biological and chemical methods, both of which include synthesis and resolution [Tetrahedron, ...

AI Technical Summary

Problems solved by technology

Although the biological method has a high optical yield, the consumption of organic solvents and water is large, the post-treatment is complicated, and the production efficiency is extremely low; while the chemical method consumes less solvent, and the atom economy in the whole process is high, but the disadvantage is that the optical selectivity is poor

The preparation of catalysts in the above synthesis processes is complex, the reaction process cycle time is long, or many experimental processes involve high temperature and high pressure conditions, low yield, low ee value, complex post-processing and other problems

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