Purifying method of (E)-2-phenyl-3-(3,5-dimethoxy-4-isopropyl benzene) crylic acid

Abstract

The invention discloses a purifying method of (E)-2-phenyl-3-(3,5-dimethoxy-4-isopropyl benzene) crylic acid and comprises two steps: 1, carrying out selective esterification on (E)-2-phenyl-3-(3,5-dimethoxy-4-isopropyl benzene) crylic acid with purity of 80-85% to obtain (E)-2-phenyl-3-(3,5-dimethoxy-4-isopropyl benzene) crylic acid a with purity of 90-95% and generating corresponding esters from impurity acids, wherein a very small quantity of corresponding esters are generated under the same reaction conditions since the product has relatively large steric hindrance and therefore the selective esterification effect is achieved; and 2, carrying out recrystallizing reaction, wherein a proper recrystallizing reagent is used and (E)-2-phenyl-3-(3,5-dimethoxy-4-isopropyl benzene) crylic acid with purity of 99% or above can be obtained. The method is applicable to purification of (E)-2-phenyl-3-(3,5-dimethoxy-4-isopropyl benzene) crylic acid and is further applicable to preparation of cis-2-(1-methylethyl)-5-[(E)-2-phenylethenyl]benzene-1,3-diol.

Description

technical field [0001] The invention belongs to the field of pharmacy, and relates to a method for purifying a cis-phenylene moder intermediate, in particular to a ( E )-2-Phenyl-3 (3,5-dimethoxy-4-isopropylbenzene) acrylic acid purification method. Background technique [0002] Benvitimod is a new generation of anti-inflammatory drugs that can be used to treat a variety of major autoimmune diseases, such as psoriasis, eczema, pyogenic colitis and various allergic diseases. Synthetic phenymod products are usually accompanied by the presence of cis-isomer impurities. [0003] Chinese invention patent application CN103992212A discloses a "synthetic method of cis-phenylene moder and application of cis-styrene moder" and provides a synthetic method of cis-styryl moder, with 3,5-dihydroxy- 4-isopropylbenzoic acid is used as raw material, and (E)-2-phenyl-3(3,5-dimethoxy-4-isopropylbenzene is prepared by methylation, reduction, oxidation and condensation methods ) crude product...

AI Technical Summary

Problems solved by technology

[0009] 3,5-dimethoxy-4-isopropyl phenylacrylic acid is prepared ( E )-2-phenyl-3(3,5-dimethoxy-4-isopropylphenyl)acrylic acid is the main impurity, and because it contains carboxyl group, its polarity is larger, and its structure is similar to ( E )-2-phenyl-3(3,5-dimethoxy-4-isopropylbenzene)acrylic acid is relatively similar, the chemical properties are relatively similar, the two cannot be separated well, and multiple recrystallization is used The method is not only for ( E )-2-phenyl-3(3,5-dimethoxy-4-isopropylphenyl)acrylic acid has a large loss and cannot obtain purity greater than 95% ( E )-2-phenyl-3(3,5-dimethoxy-4-isopropylphenyl)acrylic acid, only a small amount can be obtained by column chromatography ( E )-2-Phenyl-3(3,5-dimethoxy-4-isopropylphenyl)acrylic acid

And the method that adopts column chromatography can't realize mass production, is not suitable for the use of industrialized production; If the impurity in the condensation is not removed, after the reaction of decarboxylation and demethylation, generate corresponding 3,5-dimethoxy -4-isopropylstyrene and 3,5-dihydroxy-4-isopropylstyrene, its structure is similar to the product to be separated, and the similar properties make separation more difficult, so that the final target product yield is greatly improved reduce

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