Preparation method of optically pure 4-aryl-2-hydroxy-butyric acid

Abstract

The invention relates to a preparation method of optically pure 4-aryl-2-hydroxy-butyric acid in the technical field of chemical materials. In an organic ether or alcoholic solvent, 4-aryl-2-oxo-3-crotonic acid is catalytically hydrogenated under the coexistence of a ruthenium complex of a united aryl-axis chiral phosphine ligand and an acidic additive to prepare optically pure 4-aryl-2-hydroxy-butyric acid. Starting from the 4-aryl-2-oxo-3-crotonic acid, the invention uses the ruthenium complex of the united aryl-axis chiral phosphine ligand as a catalyst and adds the acidic additive to obtain (R)-4- aryl-2-hydroxy-butyric acid through an asymmetric catalytic hydrogenation. The invention has low cost, stable physical and chemical properties and easy purification and increases an ee value to be larger than 99 percent through a simple and convenient recrystallization method. The reaction formula is carried out as shown in the specification.

Description

technical field The invention relates to a preparation method in the technical field of chemical materials, in particular to a preparation method of optically pure 4-aryl-2-hydroxy-butyric acid. Background technique Optically pure ethyl 4-phenyl-2-hydroxy-butyrate is an important pharmaceutical intermediate and is widely used in the fields of medicine and new materials. Among them, (R)-4-phenyl-2-hydroxy-butyric acid ethyl ester is an important intermediate for the preparation of antihypertensive drugs-pril drugs. Pulil drugs are inhibitors of angiotensin-converting enzyme (ACE), and are a class of antihypertensive drugs that are currently used in a very large amount, accounting for about one-fifth of the entire hypertension drug market. Found through the retrieval of prior art document, the method for preparing (R)-4-phenyl-2-hydroxy-butyric acid ethyl ester is a lot (Asymmetric Catalysis on Industrial Scale: Challenges, Approaches and Solutions; Wiley-VCH: Weinheim , 20...

AI Technical Summary

Problems solved by technology

However, this asymmetric reaction needs to first esterify the initial raw material 4-phenyl-2-carbonyl-3-butenoate, and then use a chiral ruthenium catalyst for asymmetric hydrogenation to obtain chiral ethyl butyrate (ee: 94 %), in order to further improve the ee value of the product, the chiral product ethyl butyrate is hydrolyzed into butyric acid, the ee value is increased to more than 99% by recrystallization, and esterified again into optically pure ethyl butyrate, the whole operation process Become cumbersome, increase cost and reduce overall yield (J.Org.Chem.2008, 73, 7209)

Images