Crystallization process of D-p-hydroxyphenylglycine methyl ester

Abstract

The invention discloses a crystallization process of D-p-hydroxyphenylglycine methyl ester. The crystallization process comprises the following steps: (1) esterification reaction; (2) preparing a reaction solution; (3) crystallizing the D-p-hydroxyphenylglycine methyl ester; a finished product can be obtained; according to the method, the requirement on equipment in production is reduced, the reaction liquid is added into the deionized water reaction carrier at the same time, and the reaction liquid and the deionized water reaction carrier control the dripping speed, so that the reaction can be effectively and fully performed, the phenomenon that one reactant is excessive and needs to be recycled at the tail section of the reaction is avoided, the crystallization yield is remarkably improved, and meanwhile, the impurity content of a finished product is also reduced.

Description

Technical Field

[0001] The invention belongs to the technical field of wastewater treatment, in particular to a crystallization process of D-p-hydroxyphenylglycine methyl ester. Background Art

[0002] D-p-hydroxyphenylglycine methyl ester is a key raw material for the synthesis of semi-synthetic penicillin, amoxicillin, cefadroxil and other antibiotics. These antibiotics have broad-spectrum antibacterial and anti-inflammatory effects and have achieved significant therapeutic effects in clinical treatment. D-p-hydroxyphenylglycine methyl ester is mainly used in the field of pharmaceutical and chemical industry, especially in the synthesis of antibiotics. With the continuous advancement of medical technology and the increasing demand for health, the market demand for D-p-hydroxyphenylglycine methyl ester will continue to grow.

[0003] The traditional crystallization process of D-p-hydroxyphenylglycine methyl ester mostly uses an acidic liquid as a reaction carrier, into which an alkaline solution is dripped for reaction crystallization. This process not only has a low raw material utilization rate, but also the crystallization rate can often only reach about 90%, which needs to be improved. Summary of the invention

[0004] The purpose of the present invention is to provide a crystallization process of D-p-hydroxyphenylglycine methyl ester to solve the deficiencies in the prior art.

[0005] The technical solution adopted by the present invention is as follows: A crystallization process of D-p-hydroxyphenylglycine methyl ester comprises the following steps: (1) Esterification reaction: D-p-hydroxyphenylglycine and methanol are subjected to esterification reaction in a reactor under concentrated hydrochloric acid conditions to obtain D-p-hydroxyphenylglycine methyl ester hydrochloride; (2) Preparation of reaction solution: the D-p-hydroxyphenylglycine methyl ester hydrochloride prepared in step (1) is mixed with a hydrochloric acid solution to obtain a reaction solution A, aqueous ammonia is prepared as a reaction solution B, and a reaction kettle is prepared and deionized water is added therein as a reaction carrier; (3) Crystallization of D-p-hydroxyphenylglycine methyl ester: The reaction solution A and the reaction solution B prepared in step (2) are added into the reaction carrier at the same time, the pH value is controlled to be within the specified range, and after adding the seed crystal, the reaction solution A and the reaction solution B are continued to crystallize.

[0006] Preferably, the concentrated hydrochloric acid in step (1) has a mass fraction of 30% to 35%.

[0007] Preferably, during the reaction of the reaction solution A and the reaction solution in step (3), the pH value is controlled within the range of 5.5-6.5; Preferably, the amount of seed crystals added in step (3) is 2%-5% of the total mass of reaction solution A and reaction solution B.

[0008] Beneficial effects of the present invention: During the treatment process of the crystallization process of the present invention, the traditional method of using an acidic liquid as a reaction carrier is abandoned, which not only reduces the requirements on equipment in production, but also because the reaction liquid is added to the deionized water reaction carrier at the same time, the dripping rate of the two is controlled to effectively react fully, avoiding the phenomenon that one side of the reactant has excess and needs to be recovered at the end of the reaction, and significantly improves the crystallization yield, while also reducing the impurity content of the finished product. DETAILED DESCRIPTION Example 1

[0009] A crystallization process of D-p-hydroxyphenylglycine methyl ester comprises the following steps: (1) Esterification reaction: D-p-hydroxyphenylglycine and methanol are subjected to esterification reaction in a reactor under concentrated hydrochloric acid conditions to obtain D-p-hydroxyphenylglycine methyl ester hydrochloride; (2) Preparation of reaction solution: the D-p-hydroxyphenylglycine methyl ester hydrochloride prepared in step (1) is mixed with a hydrochloric acid solution to obtain a reaction solution A, aqueous ammonia is prepared as a reaction solution B, and a reaction kettle is prepared and deionized water is added therein as a reaction carrier; (3) Crystallization of D-p-hydroxyphenylglycine methyl ester: The reaction solution A and the reaction solution B prepared in step (2) are added into the reaction carrier at the same time, the pH value is controlled to be within the specified range, and after adding the seed crystal, the reaction solution A and the reaction solution B are continued to crystallize.

[0010] The concentration of concentrated hydrochloric acid in step (1) is 30% by mass; In step (3), during the reaction of the reaction solution A and the reaction solution, the pH value is controlled within the range of 5.5; The amount of seed crystals added in step (3) is 2% of the total mass of reaction solution A and reaction solution B. Example 2

[0011] A crystallization process of D-p-hydroxyphenylglycine methyl ester, characterized in that it comprises the following steps: (1) Esterification reaction: D-p-hydroxyphenylglycine and methanol are subjected to esterification reaction in a reactor under concentrated hydrochloric acid conditions to obtain D-p-hydroxyphenylglycine methyl ester hydrochloride; (2) Preparation of reaction solution: the D-p-hydroxyphenylglycine methyl ester hydrochloride prepared in step (1) is mixed with a hydrochloric acid solution to obtain a reaction solution A, aqueous ammonia is prepared as a reaction solution B, and a reaction kettle is prepared and deionized water is added therein as a reaction carrier; (3) Crystallization of D-p-hydroxyphenylglycine methyl ester: The reaction solution A and the reaction solution B prepared in step (2) are added into the reaction carrier at the same time, the pH value is controlled to be within the specified range, and after adding the seed crystal, the reaction solution A and the reaction solution B are continued to crystallize.

[0012] The concentration of concentrated hydrochloric acid in step (1) is 32% by mass; In step (3), during the reaction of the reaction solution A and the reaction solution, the pH value is controlled within the range of 6; The amount of seed crystals added in step (3) is 3.5% of the total mass of reaction solution A and reaction solution B. Example 3

[0013] A crystallization process of D-p-hydroxyphenylglycine methyl ester, characterized in that it comprises the following steps: (1) Esterification reaction: D-p-hydroxyphenylglycine and methanol are subjected to esterification reaction in a reactor under concentrated hydrochloric acid conditions to obtain D-p-hydroxyphenylglycine methyl ester hydrochloride; (2) Preparation of reaction solution: the D-p-hydroxyphenylglycine methyl ester hydrochloride prepared in step (1) is mixed with a hydrochloric acid solution to obtain a reaction solution A, aqueous ammonia is prepared as a reaction solution B, and a reaction kettle is prepared and deionized water is added therein as a reaction carrier; (3) Crystallization of D-p-hydroxyphenylglycine methyl ester: The reaction solution A and the reaction solution B prepared in step (2) are added into the reaction carrier at the same time, the pH value is controlled to be within the specified range, and after adding the seed crystal, the reaction solution A and the reaction solution B are continued to crystallize.

[0014] The concentration of concentrated hydrochloric acid in step (1) is 35% by mass; In step (3), during the reaction of reaction solution A and reaction solution, the pH value is controlled within the range of 6.5; The amount of seed crystals added in step (3) is 5% of the total mass of reaction solution A and reaction solution B.

[0015] Comparative Example 1 The traditional process is adopted, and an acidic liquid is used as a reaction carrier, into which an alkaline solution is dripped to carry out reaction crystallization.

[0016] The specific indicators for comparison are:

[0017] It can be seen from the above table that the crystallization of D-p-hydroxyphenylglycine methyl ester prepared by the present invention not only has a greatly improved yield, but also has a reduced impurity content, indicating that the components are fully reacted during the reaction.

[0018] The above description is only a preferred embodiment of the present invention, but the present invention does not limit the scope of implementation. Any changes made in accordance with the concept of the present invention, or modifications to equivalent embodiments with equivalent changes, which still do not exceed the spirit covered by the description and embodiments, should be within the protection scope of the present invention.

Claims

1. A crystallization process for D-p-hydroxyphenylglycine methyl ester, characterized in that: The following steps are involved: (1) Esterification reaction: D-p-hydroxyphenylglycine and methanol are subjected to esterification reaction in a reactor under concentrated hydrochloric acid conditions to obtain D-p-hydroxyphenylglycine methyl ester hydrochloride; (2) Preparation of reaction solution: the D-p-hydroxyphenylglycine methyl ester hydrochloride prepared in step (1) is mixed with a hydrochloric acid solution to obtain a reaction solution A, aqueous ammonia is prepared as a reaction solution B, and a reaction kettle is prepared and deionized water is added therein as a reaction carrier; (3) Crystallization of D-p-hydroxyphenylglycine methyl ester: The reaction solution A and the reaction solution B prepared in step (2) are added into the reaction carrier at the same time, the pH value is controlled to be within the specified range, and after adding the seed crystal, the reaction solution A and the reaction solution B are continued to crystallize.

2. A crystallization process for D-p-hydroxyphenylglycine methyl ester according to claim 1, characterized in that: The concentration of concentrated hydrochloric acid in step (1) is 30%-35% by mass.

3. A crystallization process for D-p-hydroxyphenylglycine methyl ester according to claim 1, characterized in that: During the reaction of the reaction solution A and the reaction solution in step (3), the pH value is controlled in the range of 5.5-6.

5.

4. A crystallization process for D-p-hydroxyphenylglycine methyl ester according to claim 1, characterized in that: The amount of seed crystals added in step (3) is 2%-5% of the total mass of reaction solution A and reaction solution B.

Images