Synthetic method for p-hydroxyphenyl glycine

Abstract

The invention provides a synthetic method for p-hydroxyphenyl glycine. The synthetic method includes the following steps that firstly, para-hydroxyphenyl glycine and a resolving agent are mixed for a reaction, and double salt formed by the p-hydroxyphenyl glycine and the resolving agent is obtained; secondly, the double salt formed by the p-hydroxyphenyl glycine and the resolving agent is dissolved into water and mixed with alkali liquor, and the p-hydroxyphenyl glycine is obtained through stirring, devitrifying and refining, and the p-hydroxyphenyl glycine is obtained; the resolving agent is divided into de-mandelic acid or de-phenyl ethanesulfonic acid. According to the synthetic method for the p-hydroxyphenyl glycine, the de-mandelic acid or the de-phenyl ethanesulfonic acid serves as the resolving agent, the para-hydroxyphenyl glycine is resolved, and the p-hydroxyphenyl glycine is obtained. According to the synthetic method, the synthetic technology is simple, the sources of the resolving agent are wide, cost is low, and the conversion rate on the p-hydroxyphenyl glycine is high. In addition, mother liquid formed through the synthetic method can be sustainably used after racemization, the waste water generation amount is reduced, and materials and inorganic salt in the waste water are recycled.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a synthesis method of L-p-hydroxyphenylglycine. Background technique [0002] L-p-Hydroxyphenylglycine is an important pharmaceutical intermediate, mainly used in the semi-synthesis of β-lactam antibiotics. L-p-hydroxyphenylglycine is an unnatural amino acid, which must be obtained through artificial synthesis. The synthesis method can be roughly divided into two categories: one is the biological enzyme catalysis method, which selectively synthesizes D-HPG. This method has high selectivity and the route Short, but due to the problem of biological bacteria cultivation, and the production process of raw material p-hydroxybenzene hydantoin will produce a large amount of phenol-containing wastewater, it is difficult to make large-scale industrial production; the second method is the induced crystallization resolution synthesis method, such as: the application number is ...

AI Technical Summary

Problems solved by technology

L-p-hydroxyphenylglycine is an unnatural amino acid, which must be obtained through artificial synthesis. The synthesis method can be roughly divided into two categories: one is the biological enzyme catalysis method, which selectively synthesizes D-HPG. This method has high selectivity and the route Short, but due to the problem of biological bacteria cultivation, and the production process of raw material p-hydroxybenzene hydantoin will produce a large amount of phenol-containing wastewater, it is difficult to make large-scale industrial production; the second method is the induced crystallization resolution synthesis method, such as: the application number is The patents of WO2009 / 127446, EP0530879A1, EP0450684A1, CN200810054625.0, CN92402863.6 and CN200610025197.X disclose the chemical synthesis and resolution of DL-HPG respectively. The method first prepares the mixed-rotating p-hydroxyphenylglycine, and then induces crystallization L-p-Hydroxyphenylglycine was obtained through resolution of the mother liquor, and the conversion rate from mixed-rotation p-Hydroxyphenylglycine to L-p-Hydroxyphenylglycine was 83%. The method adopted, but there are many disadvantages in the production of this split method, such as long steps, low production capacity, large turnover of solid materials, low conversion rate, etc., and high production cost

[0003] The Chinese patent with the application number CN102757156A discloses a method for synthesizing L-p-hydroxyphenylglycine from mixed-rotational p-hydroxyphenylglycine. Through integrated resolution and racemization, L-p-hydroxyphenylglycine and mixed-rotational p-hydroxyphenylglycine are obtained. To the one-pass conversion rate of L-p-hydroxyphenylglycine is 80%, which simplifies the technical process, but adopting this method to produce L-p-hydroxyphenylglycine, because of dropping into the racemization catalyst salicylaldehyde in a large amount in the mother liquor, continuous application will produce a large amount of due to salicylaldehyde The colored impurities produced by aldehyde oxidation seriously affect the product quality, resulting in high light absorption value, low conversion rate and high cost

When the mother liquor of this method is applied mechanically for more than five times, the light absorption value of the product will exceed the qualified index, and the elimination of mother liquor will be large, resulting in a large amount of waste water containing inorganic salts and organic impurities.

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