Method for recovering mother liquor of d-p-hydroxyphenylglycine methyl ester

Abstract

The present application relates to a method for recovering D-p-hydroxyphenylglycine methyl ester mother liquor, which comprises the following steps: using nanofiltration membrane to concentrate the D-p-hydroxyphenylglycine methyl ester mother liquor, then using purified water to wash the concentrated mother liquor to fully remove alcohol and salt, collecting the dialysate and recovering methanol after distillation; using macroporous adsorption resin to concentrate the nanofiltration concentrated mother liquor, wherein the D-p-hydroxyphenylglycine methyl ester is adsorbed by the macroporous adsorption resin, while the D-p-hydroxyphenylglycine is not adsorbed by the macroporous adsorption resin, and flows through the macroporous adsorption resin with the mother liquor to be collected as the adsorption residual liquid, so as to realize the separation and recovery of the D-p-hydroxyphenylglycine methyl ester and the D-p-hydroxyphenylglycine. The method can effectively recover the D-p-hydroxyphenylglycine and the D-p-hydroxyphenylglycine methyl ester from the D-p-hydroxyphenylglycine methyl ester mother liquor, and the product quality is good, which has important economic and environmental protection significance.

Description

Technical Field

[0001] This invention belongs to the field of organic chemical technology and relates to a method for recovering and treating D-p-hydroxyphenylglycine methyl ester mother liquor. More specifically, this invention relates to a method for effectively recovering D-p-hydroxyphenylglycine and D-p-hydroxyphenylglycine methyl ester from D-p-hydroxyphenylglycine methyl ester mother liquor. Background Technology

[0002] D-p-hydroxyphenylglycine methyl ester is an important intermediate in antibiotic synthesis. As an acyl side chain donor, it is used in the enzymatic synthesis of the broad-spectrum antibiotic amoxicillin. Typically, under the catalysis of immobilized penicillin acylase, D-p-hydroxyphenylglycine methyl ester condenses with 6-aminopenicillanic acid to generate amoxicillin.

[0003] D-p-hydroxyphenylglycine methyl ester can usually be prepared by esterification of D-p-hydroxyphenylglycine with methanol under suitable temperature conditions and in the presence of a catalyst. For example, at a suitable temperature, in the presence of thionyl chloride, D-p-hydroxyphenylglycine undergoes an esterification reaction with methanol. After the reaction is complete, the solution is acidic. During the reaction, a certain amount of the metal chelating agent EDTA is added, and then ammonia is added to adjust the pH of the reaction system to 7.0–8.0. After crystallization, crystal growth, filtration, and drying, D-p-hydroxyphenylglycine methyl ester crystals are obtained. The collected filtrate is the D-p-hydroxyphenylglycine methyl ester mother liquor. The concentration of D-p-hydroxyphenylglycine methyl ester is generally 1.5–3.0 g / L, the concentration of D-p-hydroxyphenylglycine is 2.0–3.0 g / L, the concentration of ammonium chloride is 70–80 g / L, the concentration of sodium sulfate is 1.5–2.0 g / L, the methanol content is 15 wt%–20 wt%, the pH is 7.0–8.0, and the conductivity is 100–130 mS / cm.

[0004] The synthesis of D-p-hydroxyphenylglycine methyl ester generates a large amount of the aforementioned mother liquor, which still contains significant amounts of D-p-hydroxyphenylglycine, D-p-hydroxyphenylglycine methyl ester, inorganic salts, and methanol. Currently, production methods only recover methanol from the mother liquor through distillation, neglecting the recovery of other effective components. This not only wastes resources but also increases the discharge of high-concentration wastewater, failing to achieve environmentally friendly and clean green production of antibiotic side chains. Therefore, researching a comprehensive recovery method for effectively recovering D-p-hydroxyphenylglycine and D-p-hydroxyphenylglycine methyl ester from the D-p-hydroxyphenylglycine methyl ester mother liquor is of significant economic and environmental importance. Summary of the Invention

[0005] Therefore, the purpose of this invention is to provide a method for recovering and treating D-p-hydroxyphenylglycine methyl ester mother liquor with reasonable process design and simple operation. This method can effectively recover D-p-hydroxyphenylglycine and D-p-hydroxyphenylglycine methyl ester from D-p-hydroxyphenylglycine methyl ester mother liquor, and the product quality is good.

[0006] To achieve the above-mentioned objectives of this invention, the technical solution adopted by this invention is as follows: The mother liquor of D-p-hydroxyphenylglycine methyl ester is concentrated by nanofiltration using a nanofiltration membrane. Then, the concentrated mother liquor is washed with purified water to fully remove alcohol and salt. The collected dialysate is distilled to recover methanol. The concentrated mother liquor is passed through a macroporous adsorption resin. D-p-hydroxyphenylglycine methyl ester is adsorbed by the macroporous adsorption resin, while D-p-hydroxyphenylglycine is not adsorbed and flows through the macroporous adsorption resin with the mother liquor, being collected as adsorption residue. This achieves the separation of D-p-hydroxyphenylglycine methyl ester and D-p-hydroxyphenylglycine.

[0007] According to the present invention, the method for recovering and treating the mother liquor of D-p-hydroxyphenylglycine methyl ester includes the following steps:

[0008] (1) Nanofiltration concentration and water washing of D-p-hydroxyphenylglycine methyl ester mother liquor

[0009] The D-p-hydroxyphenylglycine methyl ester mother liquor was concentrated using a nanofiltration membrane to obtain a concentrated mother liquor; then, the concentrated mother liquor was washed with purified water to remove methanol and ammonium chloride, resulting in a purified concentrated mother liquor.

[0010] (2) Recovery of D-p-hydroxyphenylglycine methyl ester

[0011] The purified concentrated mother liquor obtained in step (1) above is passed through a macroporous adsorption resin. D-p-hydroxyphenylglycine methyl ester is adsorbed onto the resin, while D-p-hydroxyphenylglycine is not adsorbed by the resin. The mother liquor flows through the resin and is collected as adsorption residue.

[0012] Then, the D-p-hydroxyphenylglycine methyl ester adsorbed on the resin was desorbed using a desorbing agent to obtain a desorbed solution. After the solvent was evaporated or evaporated under reduced pressure, D-p-hydroxyphenylglycine methyl ester was obtained from the desorbed solution.

[0013] (3) Recovery of D-p-hydroxyphenylglycine

[0014] After acidification, the adsorption residue obtained in step (2) was concentrated by vacuum distillation at a temperature of 60℃~80℃. D-p-hydroxyphenylglycine crystallized out and was filtered at this temperature to obtain D-p-hydroxyphenylglycine.

[0015] Beneficial effects

[0016] This invention uses nanofiltration to concentrate and wash the concentrated mother liquor with purified water to fully de-alcoholize and desalt, resulting in a purified concentrated mother liquor. This purified concentrated mother liquor is then passed through a macroporous adsorption resin, where D-p-hydroxyphenylglycine methyl ester is adsorbed by the macroporous adsorption resin, while D-p-hydroxyphenylglycine is not adsorbed and flows through the macroporous adsorption resin with the mother liquor, and is collected as the adsorption residue, thereby achieving the separation of D-p-hydroxyphenylglycine methyl ester and D-p-hydroxyphenylglycine.

[0017] This recycling process is safe, energy-saving, environmentally friendly, and low-cost, with high recovery rates and excellent product quality, making it highly suitable for industrial-scale application. Using the recycling method of this invention, D-p-hydroxyphenylglycine, D-p-hydroxyphenylglycine methyl ester, and ammonium chloride can be recovered from the mother liquor, not only increasing new economic benefits but also avoiding environmental damage, demonstrating significant practical value. Detailed Implementation

[0018] The following describes in more detail the method for recovering and treating the mother liquor of D-p-hydroxyphenylglycine methyl ester according to the present invention.

[0019] According to one embodiment of the present invention, in step (1) nanofiltration concentration and water washing of D-p-hydroxyphenylglycine methyl ester mother liquor, the D-p-hydroxyphenylglycine methyl ester mother liquor is concentrated by nanofiltration using a nanofiltration membrane to obtain concentrated mother liquor; then, the concentrated mother liquor is washed with purified water to remove methanol and ammonium chloride from the concentrated mother liquor to obtain purified concentrated mother liquor.

[0020] As described above, in the D-p-hydroxyphenylglycine methyl ester mother liquor, the concentration of D-p-hydroxyphenylglycine methyl ester is generally 1.5–3.0 g / L, the concentration of D-p-hydroxyphenylglycine is 2.0–3.0 g / L, the concentration of ammonium chloride is 70–80 g / L, the concentration of sodium sulfate is 1.5–2.0 g / L, the methanol content is 15 wt%–20 wt%, the pH is 7.0–8.0, and the conductivity is 100–130 mS / cm.

[0021] The nanofiltration membrane can be a nanofiltration membrane with a molecular weight cutoff of 100-300 Daltons to concentrate the D-p-hydroxyphenylglycine methyl ester mother liquor, obtaining a concentrated mother liquor. In this process, only water, most of the methanol, and ammonium chloride permeate through the nanofiltration membrane into the dialysate, while D-p-hydroxyphenylglycine, D-p-hydroxyphenylglycine methyl ester, and sodium sulfate in the mother liquor are retained in the concentrated mother liquor. The concentrated mother liquor is then washed with purified water, preferably at a volume of 3-4 times that of the concentrated mother liquor, maintaining a balance between the purified water feed rate and the dialysate outflow rate. This further ensures thorough removal of methanol and ammonium chloride from the concentrated mother liquor. After washing with purified water, a purified concentrated mother liquor is obtained. In the obtained purified concentrated mother liquor, the concentration of D-p-hydroxyphenylglycine methyl ester is generally 6.0-12.0 g / L, the concentration of D-p-hydroxyphenylglycine is 7.0-12.0 g / L, the concentration of ammonium chloride is 12.0-16.0 g / L, the concentration of sodium sulfate is 6.0-12.0 g / L, the content of methanol is 0.5 wt%-2.0 wt%, the pH is 7.0-8.0, and the conductivity is 10-30 mS / cm.

[0022] The dialysate produced during nanofiltration concentration and water washing has a methanol content of 5 wt% to 10 wt% after being combined. Methanol can be recovered by conventional technical methods, such as using a distillation column or rectification column, through distillation or vacuum distillation. The remaining liquid after removing methanol can be concentrated by reverse osmosis membrane to recover most of the water. The resulting concentrate can be concentrated by distillation to obtain ammonium chloride.

[0023] According to one embodiment of the present invention, in the recovery of D-p-hydroxyphenylglycine methyl ester in step (2), the purified concentrated mother liquor obtained in step (1) is passed through a macroporous adsorption resin, wherein D-p-hydroxyphenylglycine methyl ester is adsorbed on the resin, while D-p-hydroxyphenylglycine is not adsorbed by the resin and flows through the resin with the mother liquor and is collected as adsorption residue; then, the D-p-hydroxyphenylglycine methyl ester adsorbed on the resin is desorbed using a desorption agent to obtain a desorption solution, which is then distilled or distilled under reduced pressure to obtain D-p-hydroxyphenylglycine methyl ester.

[0024] The macroporous adsorption resin can be selected with a pore size of 10-30 nanometers, a particle size of 300-500 micrometers, and a specific surface area of ​​450-800 m². 2 The skeletal structure of the resin is a styrene-based, weakly polar macroporous adsorption resin. Any macroporous adsorption resin that meets these conditions can be used as a preferred macroporous adsorption resin in the method of this invention. More specifically, any one of the macroporous adsorption resins produced by Ningbo Zhengguang Resin Co., Ltd., namely DM130, SD-8, and CAD45, can be selected.

[0025] The macroporous adsorption resin is applied in the form of a circular resin column bed using a wet packing process. The height-to-diameter ratio (height-to-diameter ratio) of the circular resin column bed is 4 or greater. The purified concentrated mother liquor is passed through the macroporous adsorption resin column bed at a certain flow rate, preferably 0.5 to 1.0 times the total resin volume per hour. D-p-hydroxyphenylglycine methyl ester in the concentrated mother liquor is adsorbed onto the resin, while D-p-hydroxyphenylglycine and its salt are not adsorbed. The column loading is stopped when D-p-hydroxyphenylglycine methyl ester is detected at the lower outlet of the resin column. Then, purified water is used to wash the resin, preferably at a volume of 4.0 to 6.0 BV (column bed volume) and a flow rate of 1.0 to 2.0 BV / h (column bed volume per hour). Through water washing, the unadsorbed D-p-hydroxyphenylglycine and its salt on the resin column are removed, thereby ensuring the quality of the D-p-hydroxyphenylglycine methyl ester product to the greatest extent.

[0026] D-p-hydroxyphenylglycine and its salt were not adsorbed by the macroporous adsorption resin column bed. They flowed through the resin with the mother liquor and washing liquid and were collected as adsorption residue. In the collected adsorption residue, the concentration of D-p-hydroxyphenylglycine was generally 5.0-8.0 g / L, the pH was 7.0-8.0, and the conductivity was 10-20 mS / cm.

[0027] After washing the resin with purified water, D-p-hydroxyphenylglycine methyl ester adsorbed on the resin is eluented using an eluent. The eluent can be methanol, ethanol, isopropanol, or a mixture thereof, with methanol being preferred. The eluent flow rate is 1.0–2.0 times the total resin volume per hour, and the eluent dosage is 3.0–4.0 times the total resin volume. The collected effluent is the eluent solution, in which the concentration of D-p-hydroxyphenylglycine methyl ester is 30.0–40.0 g / L. The eluent solution is then distilled or subjected to vacuum distillation to remove the solvent. Specifically, when the eluent is methanol, vacuum distillation is performed at a temperature between 50°C and 60°C to remove methanol, thereby obtaining D-p-hydroxyphenylglycine methyl ester.

[0028] According to one embodiment of the present invention, in the recovery of D-p-hydroxyphenylglycine in step (3), the adsorption residue obtained in step (2) is acidified and then concentrated by vacuum distillation at a temperature of 60°C to 80°C, so that D-p-hydroxyphenylglycine crystallizes out and is filtered at this temperature to obtain D-p-hydroxyphenylglycine.

[0029] More specifically, the acidification treatment of the adsorption residue can be performed using acids known in the art, such as sulfuric acid with a concentration of 10 wt% to 15 wt% or hydrochloric acid with a concentration of 20 wt% to 30 wt%, to bring the pH of the adsorption residue to 4.5 to 5.5. Under these pH conditions, the solubility of D-p-hydroxyphenylglycine in water is at its lowest, thus ensuring a high yield recovery of D-p-hydroxyphenylglycine from the adsorption residue.

[0030] Then, the acidified adsorption residue was concentrated under reduced pressure to 25-30 times at a temperature of 60℃-80℃. Under this concentration ratio, the quality and yield of recovered D-p-hydroxyphenylglycine could be guaranteed. This is mainly because the solubility of D-p-hydroxyphenylglycine in water does not change significantly with temperature. Therefore, D-p-hydroxyphenylglycine does not undergo concentration and enrichment during the concentration process. Instead, as the concentration ratio increases, D-p-hydroxyphenylglycine gradually crystallizes out of the concentrate. In contrast, the solubility of ammonium chloride and sodium sulfate in water increases significantly with increasing temperature. Therefore, ammonium chloride and sodium sulfate undergo concentration and enrichment during the concentration process and do not crystallize out with increasing concentration ratio.

[0031] After concentration, the D-p-hydroxyphenylglycine precipitated from the concentrate is collected using conventional filtration techniques. During filtration, the temperature of the concentrate must be maintained between 60℃ and 80℃ to prevent the precipitation of ammonium chloride and sodium sulfate, which could affect the quality of the D-p-hydroxyphenylglycine product. Then, through drying, a D-p-hydroxyphenylglycine product meeting quality standards is obtained.

[0032] The mother liquor remaining after filtering and collecting D-p-hydroxyphenylglycine can be cooled to 10℃~20℃. Under this temperature condition, a large amount of ammonium chloride and sodium sulfate will crystallize out. After filtering and collecting the precipitated ammonium chloride and sodium sulfate, and drying to remove moisture, a mixed salt product is obtained.

[0033] The following examples provide a more detailed description of the method for recovering and treating the mother liquor of D-p-hydroxyphenylglycine methyl ester according to the present invention. The scope of protection of the present invention is not limited to the following examples. These examples are listed for illustrative purposes only and do not limit the present invention in any way.

[0034] Example 1

[0035] (1) Nanofiltration concentration and water washing of D-p-hydroxyphenylglycine methyl ester mother liquor

[0036] 200 L of mother liquor obtained after crystallization and separation of D-p-hydroxyphenylglycine methyl ester was taken, in which the concentration of D-p-hydroxyphenylglycine methyl ester was 2.6 g / L, the concentration of D-p-hydroxyphenylglycine was 2.1 g / L, the concentration of ammonium chloride was 75 g / L, the concentration of sodium sulfate was 1.7 g / L, the content of methanol was 15 wt%, the pH was 7.2, and the conductivity was 116 mS / cm. The concentration was concentrated to 4 times using a nanofiltration membrane with a molecular weight cutoff of 100 Daltons. Then, the concentrated mother liquor was washed with purified water at a volume of 4 times the volume of the concentrated mother liquor to obtain 50 L of purified concentrated mother liquor, in which the concentration of D-p-hydroxyphenylglycine methyl ester was 10.2 g / L, the concentration of D-p-hydroxyphenylglycine was 8.3 g / L, the concentration of ammonium chloride was 15.0 g / L, the concentration of sodium sulfate was 6.7 g / L, the content of methanol was 0.9 wt%, the pH was 7.1, and the conductivity was 22 mS / cm.

[0037] (2) Recovery of D-p-hydroxyphenylglycine methyl ester

[0038] Next, 50 L of the purified concentrated mother liquor was passed through a macroporous adsorption resin column (resin type DM130, 5 L capacity, aspect ratio 4) at a flow rate of 5 L / h. After loading, the resin was washed with 20 L of purified water at a flow rate of 10 L / h. D-p-hydroxyphenylglycine methyl ester was adsorbed onto the resin, while D-p-hydroxyphenylglycine and residual salts were not adsorbed and flowed through the resin with the mother liquor and washing liquid, and were collected as adsorption residue. The collected adsorption residue volume was 70 L, with a D-p-hydroxyphenylglycine concentration of 5.9 g / L, a pH of 7.1, and a conductivity of 16 mS / cm.

[0039] Then, methanol was used to desorb the D-p-hydroxyphenylglycine methyl ester adsorbed on the resin at a flow rate of 5 L / h. A total of 15 L of effluent was collected from this part, which is the eluent. The concentration of D-p-hydroxyphenylglycine methyl ester in this eluent is 33.5 g / L. Finally, methanol was removed from the eluent by distillation to obtain 504 g of D-p-hydroxyphenylglycine methyl ester with a purity of 99.4% and a yield of 96.9%. The specific rotation is -148.9° (c = 1, 1NHCl).

[0040] (3) Recovery of D-p-hydroxyphenylglycine

[0041] The pH of 70 L of the collected adsorption residue was adjusted to 5.0 using 25% hydrochloric acid, and the temperature was raised to 80 °C while maintaining a vacuum of ≤-0.080 MPa. Under these conditions, the solution was concentrated 30 times under reduced pressure, resulting in the crystallization of D-p-hydroxyphenylglycine. The concentrate was then filtered while still at 80 °C to obtain 370 g of D-p-hydroxyphenylglycine with a purity of 99.0% and a yield of 88.1%, with a specific rotation of -157.9° (c = 1, 1N HCl).

[0042] Example 2

[0043] (1) Nanofiltration concentration and water washing of D-p-hydroxyphenylglycine methyl ester mother liquor

[0044] 200 L of mother liquor obtained after crystallization and separation of D-p-hydroxyphenylglycine methyl ester was taken, in which the concentration of D-p-hydroxyphenylglycine methyl ester was 2.2 g / L, the concentration of D-p-hydroxyphenylglycine was 2.3 g / L, the concentration of ammonium chloride was 77 g / L, the concentration of sodium sulfate was 1.6 g / L, the content of methanol was 16 wt%, the pH was 7.3, and the conductivity was 125 mS / cm. The concentrate was then concentrated to 4 times using a nanofiltration membrane with a molecular weight cutoff of 100 Daltons. The concentrated mother liquor was then washed with purified water at a volume 4 times that of the concentrated mother liquor, yielding 50 L of purified concentrated mother liquor, in which the concentration of D-p-hydroxyphenylglycine methyl ester was 8.6 g / L, the concentration of D-p-hydroxyphenylglycine was 9.1 g / L, the concentration of ammonium chloride was 15.4 g / L, the concentration of sodium sulfate was 6.3 g / L, the content of methanol was 1.2 wt%, the pH was 7.2, and the conductivity was 26 mS / cm.

[0045] (2) Recovery of D-p-hydroxyphenylglycine methyl ester

[0046] Next, 50 L of the purified concentrated mother liquor was passed through a macroporous adsorption resin column (resin type DM130, 5 L capacity, aspect ratio 4) at a flow rate of 5 L / h. After loading, the resin was washed with 20 L of purified water at a flow rate of 10 L / h. D-p-hydroxyphenylglycine methyl ester was adsorbed onto the resin, while D-p-hydroxyphenylglycine and residual salts were not adsorbed and flowed through the resin with the mother liquor and washing liquid, and were collected as adsorption residue. The collected adsorption residue volume was 70 L, with a D-p-hydroxyphenylglycine concentration of 6.5 g / L, a pH of 7.2, and a conductivity of 19 mS / cm.

[0047] Then, methanol was used to desorb the D-p-hydroxyphenylglycine methyl ester adsorbed on the resin at a flow rate of 5 L / h. A total of 15 L of effluent was collected, which was the eluent. The concentration of D-p-hydroxyphenylglycine methyl ester was 28.7 g / L. Finally, the methanol in the eluent was removed by vacuum distillation at 50 °C to 60 °C, yielding 422 g of D-p-hydroxyphenylglycine methyl ester with a purity of 99.1% and a yield of 96.0%. The specific rotation was -148.8° (c = 1, 1N HCl).

[0048] (3) Recovery of D-p-hydroxyphenylglycine

[0049] The pH of 70 L of the collected adsorption residue was adjusted to 5.1 using 25% hydrochloric acid, and the temperature was raised to 80 °C while maintaining a vacuum of ≤-0.080 MPa. Under these conditions, the solution was concentrated 30 times under reduced pressure, resulting in the crystallization of D-p-hydroxyphenylglycine. The concentrate was then filtered while still at 80 °C to obtain 416 g of D-p-hydroxyphenylglycine with a purity of 99.1% and a yield of 90.4%, with a specific rotation of -158.0° (c = 1, 1N HCl).

[0050] Example 3

[0051] (1) Nanofiltration concentration and water washing of D-p-hydroxyphenylglycine methyl ester mother liquor

[0052] 200 L of mother liquor obtained after crystallization and separation of D-p-hydroxyphenylglycine methyl ester was taken, in which the concentration of D-p-hydroxyphenylglycine methyl ester was 1.8 g / L, the concentration of D-p-hydroxyphenylglycine was 2.7 g / L, the concentration of ammonium chloride was 76 g / L, the concentration of sodium sulfate was 1.7 g / L, the content of methanol was 16 wt%, the pH was 7.2, and the conductivity was 119 ms / cm. The concentrate was then concentrated to 4 times using a nanofiltration membrane with a molecular weight cutoff of 100 Daltons. The concentrated mother liquor was then washed with purified water at a volume 4 times that of the concentrated mother liquor, yielding 50 L of purified concentrated mother liquor, in which the concentration of D-p-hydroxyphenylglycine methyl ester was 7.1 g / L, the concentration of D-p-hydroxyphenylglycine was 10.7 g / L, the concentration of ammonium chloride was 15.2 g / L, the concentration of sodium sulfate was 6.7 g / L, the content of methanol was 1.2 wt%, the pH was 7.2, and the conductivity was 24 ms / cm.

[0053] (2) Recovery of D-p-hydroxyphenylglycine methyl ester

[0054] Next, 50 L of the purified concentrated mother liquor was passed through a macroporous adsorption resin column (resin type DM130, 5 L capacity, aspect ratio 4) at a flow rate of 5 L / h. After loading, the resin was washed with 20 L of purified water at a flow rate of 10 L / h. D-p-hydroxyphenylglycine methyl ester was adsorbed onto the resin, while D-p-hydroxyphenylglycine and residual salts were not adsorbed and flowed through the resin with the mother liquor and washing liquid, and were collected as adsorption residue. The collected adsorption residue volume was 70 L, with a D-p-hydroxyphenylglycine concentration of 7.6 g / L, a pH of 7.2, and a conductivity of 17 mS / cm.

[0055] Then, methanol was used to desorb the D-p-hydroxyphenylglycine methyl ester adsorbed on the resin at a flow rate of 5 L / h. A total of 15 L of effluent was collected, which was the eluent. The concentration of D-p-hydroxyphenylglycine methyl ester was 23.5 g / L. Finally, the methanol in the eluent was removed by vacuum distillation at 50 °C to 60 °C, yielding 346 g of D-p-hydroxyphenylglycine methyl ester with a purity of 99.2% and a yield of 96.0%. The specific rotation was -148.8° (c = 1, 1N HCl).

[0056] (3) Recovery of D-p-hydroxyphenylglycine

[0057] The pH of 70 L of the collected adsorption residue was adjusted to 5.0 using 25% hydrochloric acid, and the temperature was raised to 80 °C while the vacuum degree was controlled at ≤-0.080 MPa. Under these conditions, the solution was concentrated 30 times under reduced pressure, and D-p-hydroxyphenylglycine crystallized out. The concentrate was filtered while hot at 80 °C to obtain 497 g of D-p-hydroxyphenylglycine with a purity of 99.2% and a yield of 92.1%, and a specific rotation of -158.2° (c=1, 1N HCl).

Claims

1. A method for recovering and treating the mother liquor of D-p-hydroxyphenylglycine methyl ester, comprising the following steps: (1) Nanofiltration concentration and water washing of D-p-hydroxyphenylglycine methyl ester mother liquor The D-p-hydroxyphenylglycine methyl ester mother liquor was concentrated using a nanofiltration membrane to obtain a concentrated mother liquor; then, the concentrated mother liquor was washed with purified water to remove methanol and ammonium chloride, resulting in a purified concentrated mother liquor. (2) Recovery of D-p-hydroxyphenylglycine methyl ester The purified concentrated mother liquor obtained in step (1) above is passed through a macroporous adsorption resin. D-p-hydroxyphenylglycine methyl ester is adsorbed onto the resin, while D-p-hydroxyphenylglycine is not adsorbed by the resin. The mother liquor flows through the resin and is collected as adsorption residue. Then, the D-p-hydroxyphenylglycine methyl ester adsorbed on the resin was desorbed using a desorbing agent to obtain a desorbed solution. After the solvent was evaporated or evaporated under reduced pressure, D-p-hydroxyphenylglycine methyl ester was obtained from the desorbed solution. (3) Recovery of D-p-hydroxyphenylglycine The adsorption residue obtained in step (2) above was acidified and then concentrated by vacuum distillation at a temperature of 60℃~80℃. D-p-hydroxyphenylglycine crystallized out and was filtered at this temperature to obtain D-p-hydroxyphenylglycine. in, In the D-p-hydroxyphenylglycine methyl ester mother liquor, the concentration of D-p-hydroxyphenylglycine methyl ester is 1.5–3.0 g / L, the concentration of D-p-hydroxyphenylglycine is 2.0–3.0 g / L, the concentration of ammonium chloride is 70–80 g / L, the concentration of sodium sulfate is 1.5–2.0 g / L, the methanol content is 15 wt%–20 wt%, the pH is 7.0–8.0, and the conductivity is 100–130 mS / cm. In the nanofiltration concentration and water washing of the D-p-hydroxyphenylglycine methyl ester mother liquor in step (1), the amount of purified water used is 3 to 4 times the volume of the concentrated mother liquor, and the flow rate of purified water feed and the flow rate of dialysate are kept in balance to remove methanol and ammonium chloride from the concentrated mother liquor and obtain purified concentrated mother liquor. In step (2) of the recovery of D-p-hydroxyphenylglycine methyl ester, the macroporous adsorption resin is selected with a pore size of 10-30 nanometers, a particle size of 300-500 micrometers, and a specific surface area of ​​450-800 m². 2 The skeleton structure of / g is a styrene-based weakly polar macroporous adsorption resin; the desorbent is methanol, ethanol, isopropanol or a mixture thereof; In step (3) recovery of D-p-hydroxyphenylglycine, the above-acidified adsorption residue is concentrated under reduced pressure to 25-30 times at a temperature of 60℃~80℃. After concentration, the D-p-hydroxyphenylglycine precipitated in the concentrate is collected by filtration, and the temperature of the concentrate is maintained in the range of 60℃~80℃ during the filtration and collection process.

2. The method for recovering and treating the mother liquor of D-p-hydroxyphenylglycine methyl ester according to claim 1, characterized in that, in In step (1) of nanofiltration concentration and water washing of D-p-hydroxyphenylglycine methyl ester mother liquor, the nanofiltration membrane is a nanofiltration membrane with a molecular weight cutoff of 100 to 300 Daltons.

3. The method for recovering and treating the mother liquor of D-p-hydroxyphenylglycine methyl ester according to claim 1, characterized in that, in The purified concentrated mother liquor contained D-p-hydroxyphenylglycine methyl ester at a concentration of 6.0–12.0 g / L, D-p-hydroxyphenylglycine at a concentration of 7.0–12.0 g / L, ammonium chloride at a concentration of 12.0–16.0 g / L, sodium sulfate at a concentration of 6.0–12.0 g / L, methanol at a content of 0.5 wt%–2.0 wt%, pH at a concentration of 7.0–8.0, and conductivity at a concentration of 10–30 mS / cm.

4. The method for recovering and treating the mother liquor of D-p-hydroxyphenylglycine methyl ester according to claim 1, characterized in that, in In step (2) recovery of D-p-hydroxyphenylglycine methyl ester, the macroporous adsorption resin is selected from any one of the following macroporous adsorption resins produced by Ningbo Zhengguang Resin Co., Ltd.: DM130, SD-8 and CAD45.

5. The method for recovering and treating the mother liquor of D-p-hydroxyphenylglycine methyl ester according to claim 1, characterized in that, in In step (2) of the recovery of D-p-hydroxyphenylglycine methyl ester, the macroporous adsorption resin is applied in the form of a circular resin column bed using wet packing, and the height-to-diameter ratio of the circular resin column bed is 4 or greater. The purified concentrated mother liquor is passed through the resin column bed at a flow rate of 0.5 to 1.0 times the total resin volume per hour. D-p-hydroxyphenylglycine methyl ester in the concentrated mother liquor is adsorbed onto the resin, while D-p-hydroxyphenylglycine and its salt are not adsorbed by the resin. When D-p-hydroxyphenylglycine is present at the lower outlet of the resin column bed... The column loading was stopped when glycine methyl ester was detected; then the resin was washed with purified water at a volume of 4.0–6.0 BV and a flow rate of 1.0–2.0 BV / h. D-p-hydroxyphenylglycine and its salt were not adsorbed by the macroporous adsorption resin column bed and flowed through the resin with the mother liquor and washing liquid and were collected as adsorption residue. In the collected adsorption residue, the concentration of D-p-hydroxyphenylglycine was 5.0–8.0 g / L, the pH was 7.0–8.0, and the conductivity was 10–20 mS / cm.

6. The method for recovering and treating the mother liquor of D-p-hydroxyphenylglycine methyl ester according to claim 5, characterized in that, in In step (2) recovery of D-p-hydroxyphenylglycine methyl ester, after washing the resin with purified water, an eluent is used to elute the D-p-hydroxyphenylglycine methyl ester adsorbed on the resin. The eluent flow rate is 1.0 to 2.0 times the total resin volume per hour, and the eluent dosage is 3.0 to 4.0 times the total resin volume. The effluent collected here is the eluent, in which the concentration of D-p-hydroxyphenylglycine methyl ester is 30.0 to 40.0 g / L.

7. The method for recovering and treating the mother liquor of D-p-hydroxyphenylglycine methyl ester according to claim 1, characterized in that, in In step (3) of the recovery of D-p-hydroxyphenylglycine, the adsorption residue is acidified by using sulfuric acid or hydrochloric acid, so that the pH of the adsorption residue is 4.5 to 5.5 after acidification.