A process for the preparation of R-(+)-2-(4-hydroxyphenoxy)propionic acid

Abstract

The application relates to a preparation method of R-(+)-2-(4-hydroxyphenoxy)propionic acid and belongs to the technical field of medicines and chemical industry. The preparation method of the R-(+)-2-(4-hydroxyphenoxy)propionic acid takes s-2 chloropropionic acid as raw material, generates a sodium salt by reacting with sodium hydroxide, reacts with hydroquinone, extracts by using an R211 extracting agent, and obtains R-2-(4-hydroxyphenoxy)propionic acid. The prepared R-(+)-2-(4-hydroxyphenoxy)propionic acid has very high purity, the purity of the final product is stable and reaches 99.8% (the national standard is 99.5%), the optical purity is simultaneously greatly improved, the yield is improved, after replacing the activated carbon process, the physical adsorption loss is reduced, the comprehensive yield is improved by about 1.8%, it is green and continuous, the extracting agent can be recycled, no waste carbon is generated, a multi-section rotary column supports continuous operation, and the production efficiency is improved by 3 times.

Description

Technical Field

[0001] This invention relates to a method for preparing R-(+)-2-(4-hydroxyphenoxy)propionic acid, belonging to the field of pharmaceutical and chemical technology. Background Technology

[0002] R-(+)-2-(4-hydroxyphenoxy)propionic acid is prepared by the etherification reaction of sodium salt of S-2-chloropropionate with hydroquinone. The traditional process in the later stage of this reaction mainly uses activated carbon adsorption decolorization combined with recrystallization for purification. That is, after the reaction, a large amount of activated carbon is added to the system to adsorb pigments and by-product impurities. After filtration, the pH value is adjusted and the crystallization is carried out by cooling multiple times to obtain R-(+)-2-(4-hydroxyphenoxy)propionic acid with a certain purity. However, this method has the following defects: (1) Impurities are not completely removed. Activated carbon adsorption is blind and has limited effect on the separation of isomers with similar properties and organic micro-impurities. The purity of the product is usually difficult to consistently exceed 99.5%. (2) The yield loss is large. Activated carbon adsorption will cause about 2% to 5% of the target product to be physically carried away and lost. Multiple crystallization will result in a large amount of product remaining in the mother liquor, resulting in significant yield loss. (3) The production continuity is poor. Filtering activated carbon is an intermittent operation with high labor intensity and is prone to generating a large amount of solid waste (waste carbon), which puts great pressure on environmental protection. (4) Limited optical rotation performance: Traditional processes are not capable of removing residual chiral impurities, resulting in large fluctuations in the optical purity (optical rotation) of the final product.

[0003] Therefore, there is a need to provide an efficient extraction and purification process for R-(+)-2-(4-hydroxyphenoxy)propionic acid to solve the technical problems of product purity bottleneck, high yield loss and unstable optical rotation performance in traditional processes. Summary of the Invention

[0004] To overcome the shortcomings of existing technologies, the present invention aims to provide a highly efficient extraction and purification scheme. By coupling a specialized extractant with a multi-segment rotary extraction column, it solves the technical problems of product purity bottlenecks, high yield losses, and unstable optical rotation performance in traditional processes. S-2-chloropropionic acid is used as a raw material to form a salt with sodium hydroxide, followed by an etherification reaction to obtain a crude solution. This solution is then purified by countercurrent extraction using a multi-segment rotary extraction modified purification column with a specialized extractant, R211.

[0005] To achieve the above objectives, the technical solution adopted by the present invention is as follows: a method for preparing R-(+)-2-(4-hydroxyphenoxy)propionic acid, characterized in that, in the preparation process of R-(+)-2-(4-hydroxyphenoxy)propionic acid, R211 extractant is used for extraction, and the specific extraction steps are as follows: (1) Preparation of the solution to be treated: After preliminary neutralization, the etherification reaction solution is adjusted to a specific concentration; (2) Continuous extraction: The liquid to be processed enters from the top of the purification column, and the R211 extractant enters countercurrently from the bottom of the column, with the rotation speed controlled at 100-300 rpm; (3) Gradient elution: using the shear force generated by multi-stage rotation, impurities are enriched in the raffinate and discharged, while the target product enters the extraction phase; (4) Back-extraction and crystallization: After the extract phase is back-extracted by a weak alkaline solution, it is directly crystallized by adjusting the acid.

[0006] As a preferred embodiment of the preparation method of R-(+)-2-(4-hydroxyphenoxy)propionic acid according to the present invention, the R-(+)-2-(4-hydroxyphenoxy)propionic acid is prepared by using S-2-chloropropionic acid as a raw material, reacting it with sodium hydroxide to form a sodium salt, reacting it with hydroquinone, and extracting it with R211 extractant to obtain R-2-(4-hydroxyphenoxy)propionic acid.

[0007] In a preferred embodiment of the preparation method of R-(+)-2-(4-hydroxyphenoxy)propionic acid according to the present invention, in step (1), the etherification reaction solution is an aqueous mixture obtained by sodium salting of S-2-chloropropionic acid and etherification reaction with hydroquinone, the pH is adjusted to 3.5-4.5, the mass concentration of the aqueous mixture is adjusted to 80-150 g / L, and the temperature is controlled at 40-60℃.

[0008] As a preferred embodiment of the preparation method of R-(+)-2-(4-hydroxyphenoxy)propionic acid according to the present invention, in step (2), the purification column is a multi-segment rotary extraction modified purification column, and the R211 extractant, by mass percentage, includes 40%~60% main extractant, 10%~20% co-extraction aid, and 20%~40% diluent.

[0009] As a preferred embodiment of the preparation method of R-(+)-2-(4-hydroxyphenoxy)propionic acid according to the present invention, the multi-stage rotary extraction modified purification column includes a multi-stage rotor structure, a modified packing layer, and a laminar flow regulating plate.

[0010] As a preferred embodiment of the preparation method of R-(+)-2-(4-hydroxyphenoxy)propionic acid according to the present invention, the multi-stage rotor structure is that the column of the multi-segment rotary extraction modification and purification column is provided with 5-10 independently rotating stirring plates inside the column, and the speed is adjusted by a variable frequency motor. The modified packing layer consists of a special polytetrafluoroethylene modified wire mesh packing material placed behind each stirring section of the multi-segment rotary extraction modified purification column. The laminar flow control plate utilizes the difference in flow rate of different components within the column to achieve "chromatographic-grade" enrichment and separation of the target product and trace impurities.

[0011] In a preferred embodiment of the method for preparing R-(+)-2-(4-hydroxyphenoxy)propionic acid according to the present invention, the main extractant is selected from a modified mixture of methyl isobutyl ketone or tributyl phosphate; the co-extraction aid is a higher fatty alcohol; and the diluent is an alkane or cyclohexane.

[0012] In a preferred embodiment of the method for preparing R-(+)-2-(4-hydroxyphenoxy)propionic acid according to the present invention, the higher fatty alcohol is octanol.

[0013] In a preferred embodiment of the preparation method of R-(+)-2-(4-hydroxyphenoxy)propionic acid according to the present invention, in step (3), the impurities are enriched in the raffinate and discharged by utilizing the shear force generated by multi-segment rotation, and the target product enters the extraction phase; specifically, the gradient elution operation temperature is 30-50℃, the volume ratio of extractant to feed liquid is 1:3-5, the rotation speed is 100-300 rpm, the number of gradient segments is 5-10, and the target product content in the raffinate is ≤0.5% (HPLC method) as the elution endpoint judgment standard.

[0014] In a preferred embodiment of the preparation method of R-(+)-2-(4-hydroxyphenoxy)propionic acid according to the present invention, in step (4), after the extract phase is back-extracted by a weak alkaline solution, it is directly crystallized by adjusting the acid. Specifically, the alkaline solution used for back-extraction is a sodium carbonate aqueous solution with a mass fraction of 3-8%, the amount of which is 0.3-0.5 times the volume of the extract phase, the back-extraction temperature is 35-45℃, and the pH of the aqueous phase after back-extraction is 8.0-9.5. The acid solution used for acid-adjusted crystallization is a hydrochloric acid aqueous solution with a mass fraction of 20-30%, the pH is adjusted to 2.5-3.5, and the crystallization is carried out at 5-15℃ for 1-2 h. The target product is obtained by centrifugation, washing, and drying.

[0015] The method for preparing R-(+)-2-(4-hydroxyphenoxy)propionic acid uses s-2-chloropropionic acid as a raw material, reacts with sodium hydroxide to form a sodium salt, then reacts with hydroquinone, and is extracted with R211 extractant to obtain R-2-(4-hydroxyphenoxy)propionic acid. Core formulation: R211 type special extractant. The R211 extraction system developed in this invention contains the following components (by mass percentage): Main extractant (40%~60%): a modified mixture selected from methyl isobutyl ketone (MIBK) or tributyl phosphate (TBP), with an extremely high partition coefficient for D-HPPA. Co-extraction aid (10%~20%): higher fatty alcohols (such as octanol), used to adjust interfacial tension. Diluent (20%~40%): special high flash point alkane, reducing system viscosity and accelerating two-phase separation. For low-concentration systems, the diluent can be partially replaced with cyclohexane.

[0016] The core equipment in the preparation method of R-(+)-2-(4-hydroxyphenoxy)propionic acid is a multi-stage rotary extraction modified purification column. This equipment is the structural innovation of this invention, and its specific structure includes: a multi-stage rotor structure: the column body has 5-10 independently rotating stirring discs, and the speed is adjusted by a variable frequency motor to change the droplet dispersion. A modified packing layer: each stirring section is followed by a special polytetrafluoroethylene (PTFE) modified wire mesh packing for forced polymerization and redispersion. A laminar flow regulating plate: utilizing the difference in flow rate of different components within the column (based on differences in molecular polarity and partition ratio), "chromatographic-grade" enrichment and separation of the target product and trace impurities is achieved.

[0017] The operational flow of the method for preparing R-(+)-2-(4-hydroxyphenoxy)propionic acid is as follows: Preparation of the treatment solution: After preliminary neutralization, the etherification reaction solution is adjusted to a specific concentration. Continuous extraction: The treatment solution enters from the top of the column, and the R211 extractant enters countercurrently from the bottom of the column. The rotation speed is controlled at 100-300 rpm. Gradient elution: Utilizing the shear force generated by multi-stage rotation, impurities are enriched in the raffinate and discharged, while the target product enters the extraction phase. Back-extraction and crystallization: After back-extraction with a weak alkaline solution, the extraction phase is adjusted to acid and crystallized directly.

[0018] Compared with the prior art, the beneficial effects of the present invention are as follows: The R-(+)-2-(4-hydroxyphenoxy)propionic acid prepared by the present invention: (1) Extremely high purity: The purity of the final product is consistently 99.8% (the national standard is 99.5%), and the optical purity is significantly improved simultaneously.

[0019] (2) Increased yield: After replacing the activated carbon process, the physical adsorption loss was reduced, and the overall yield was increased by about 1.8%.

[0020] (3) Green and continuous: The extractant can be recycled and no waste carbon is generated; and the multi-stage rotating column supports continuous operation, increasing production efficiency by 3 times.

[0021] (4) Precise separation: For specific etherification byproducts, precise enrichment is achieved by utilizing the difference in flow rate.

[0022] (5) Components and ratio range of R211 extractant: especially the combination of main extractant and co-extraction agent after optimization of D-HPPA molecular structure. Internal structure design of extraction modified purification column: the focus is on the combination of "multi-stage rotating disk + PTFE modified packing" and its application in the purification of chiral intermediates. Methodology of separation by flow rate difference: protect the process of adjusting the distribution of impurities by physical parameters (rotation speed, flow rate) in this specific extraction equipment. Detailed Implementation

[0023] Unless otherwise specified, the experimental methods used in the embodiments are conventional methods, and the materials and reagents used are commercially available unless otherwise specified.

[0024] Example 1: This example illustrates a method for preparing R-(+)-2-(4-hydroxyphenoxy)propionic acid according to the present invention. The R-(+)-2-(4-hydroxyphenoxy)propionic acid is prepared using R211 extractant. The specific extraction steps are as follows: (1) Preparation of the solution to be treated: Sodium salt is generated by reacting S-2 chloropropionic acid with sodium hydroxide, and then reacted with hydroquinone to obtain an aqueous phase mixture. The temperature is 40℃. The pH of the aqueous phase mixture is adjusted to 3.5 and the mass concentration is adjusted to 80g / L.

[0025] (2) Continuous extraction: The liquid to be treated enters from the top of the purification column at a flow rate of 5 L / min, and the R211 extractant enters countercurrently from the bottom of the column, with the rotation speed controlled at 100 rpm; the purification column is a multi-stage rotary extraction modified purification column, and the R211 extractant, by mass percentage, includes 40% of the modified mixture of the main extractant methyl isobutyl ketone, 10% of the co-extraction aid octanol, and 20% of the diluent alkane; the multi-stage rotary extraction modified purification column includes a multi-stage rotor structure, a modified packing layer, and a laminar flow regulating plate; the multi-stage rotor structure is that the column body of the multi-stage rotary extraction modified purification column is equipped with 5 independently rotating stirring plates, and the rotation speed is adjusted by a variable frequency motor; the modified packing layer is that each stirring section of the multi-stage rotary extraction modified purification column is equipped with special polytetrafluoroethylene modified wire mesh packing; the laminar flow regulating plate utilizes the difference in flow rate of different components in the column to achieve "chromatographic" enrichment and separation of the target product and trace impurities; (3) Gradient elution: using the shear force generated by multi-stage rotation, impurities are enriched in the raffinate and discharged, and the target product enters the extraction phase; specifically, the operating temperature of gradient elution is 30℃, the volume ratio of extractant to feed liquid is 1:3, the rotation speed is 100 rpm, the number of gradient stages is 5, and the content of target product in the raffinate is ≤0.5% (HPLC method) as the elution endpoint judgment standard.

[0026] (4) Back-extraction and crystallization: After the extract phase is back-extracted by a weak alkaline solution, it is directly crystallized by adjusting the acid. Specifically, the alkaline solution used for back-extraction is a sodium carbonate aqueous solution with a mass fraction of 3%, and the amount used is 0.3 times the volume of the extract phase. The back-extraction temperature is 35℃, and the pH of the aqueous phase after back-extraction is 8.0. The acid solution used for acid-adjusted crystallization is a hydrochloric acid aqueous solution with a mass fraction of 20%. The pH is adjusted to 2.5, and the crystallization is carried out at 5℃ for 1 hour. The target product is obtained by centrifugation, washing, and drying.

[0027] Example 2: This example illustrates a method for preparing R-(+)-2-(4-hydroxyphenoxy)propionic acid according to the present invention. The R-(+)-2-(4-hydroxyphenoxy)propionic acid is prepared using R211 extractant. The specific extraction steps are as follows: (1) Preparation of the solution to be treated: Sodium salt is generated by reacting S-2 chloropropionic acid with sodium hydroxide, and then reacted with hydroquinone to obtain an aqueous phase mixture. The temperature is controlled at 60℃, the pH is adjusted to 4.5, and the mass concentration of the aqueous phase mixture is adjusted to 150g / L. (2) Continuous extraction: The liquid to be treated enters from the top of the purification column at a flow rate of 5 L / min, and the R211 extractant enters countercurrently from the bottom of the column, with the rotation speed controlled at 300 rpm; the purification column is a multi-stage rotary extraction modified purification column, and the R211 extractant, by mass percentage, includes 60% modified mixture of the main extractant tributyl phosphate, 20% co-extraction aid octanol, and 40% diluent cyclohexane; the multi-stage rotary extraction modified purification column includes a multi-stage rotor structure, a modified packing layer, and a laminar flow regulating plate; the multi-stage rotor structure is that the column body of the multi-stage rotary extraction modified purification column is equipped with 5-10 independently rotating stirring plates, and the rotation speed is adjusted by a variable frequency motor; the modified packing layer is that each stirring section of the multi-stage rotary extraction modified purification column is equipped with special polytetrafluoroethylene modified wire mesh packing; the laminar flow regulating plate utilizes the difference in flow rate of different components in the column to achieve "chromatographic" enrichment and separation of the target product and trace impurities; (3) Gradient elution: using the shear force generated by multi-stage rotation, impurities are enriched in the raffinate and discharged, and the target product enters the extraction phase; specifically, the operating temperature of gradient elution is 50℃, the volume ratio of extractant to feed liquid is 1:5, the rotation speed is 300 rpm, the number of gradient stages is 10, and the target product content in the raffinate is ≤0.5% (HPLC method) as the elution endpoint judgment standard.

[0028] (4) Back-extraction and crystallization: After back-extraction with a weak alkaline solution, the extract phase is directly crystallized by adjusting the acid. The alkaline solution used for back-extraction is an 8% sodium carbonate aqueous solution, the amount of which is 0.5 times the volume of the extract phase. The back-extraction temperature is 45℃, and the pH of the aqueous phase after back-extraction is 9.5. The acid solution used for acid-adjusted crystallization is a 30% hydrochloric acid aqueous solution. The pH is adjusted to 3.5, and the crystallization is carried out at 15℃ for 2 hours. The target product is obtained by centrifugation, washing, and drying.

[0029] Example 3: This example illustrates a method for preparing R-(+)-2-(4-hydroxyphenoxy)propionic acid according to the present invention. The R-(+)-2-(4-hydroxyphenoxy)propionic acid is prepared using R211 extractant. The specific extraction steps are as follows: (1) Preparation of the solution to be treated: Using S-2 chloropropionic acid as raw material, sodium hydroxide is reacted to form sodium salt, and then reacted with hydroquinone to obtain an aqueous phase mixture. The temperature is controlled at 50℃, the pH is adjusted to 4, and the mass concentration of the aqueous phase mixture is adjusted to 80-150 g / L. (2) Continuous extraction: The liquid to be treated enters from the top of the purification column at a flow rate of 5 L / min, and the R211 extractant enters countercurrently from the bottom of the column, with the rotation speed controlled at 200 rpm; the purification column is a multi-stage rotary extraction modified purification column, and the R211 extractant, by mass percentage, includes 50% modified mixture of the main extractant tributyl phosphate, 15% co-extraction aid octanol, and 30% diluent cyclohexane; the multi-stage rotary extraction modified purification column includes a multi-stage rotor structure, a modified packing layer, and a laminar flow regulating plate; the multi-stage rotor structure is that the column body of the multi-stage rotary extraction modified purification column is equipped with 6 independently rotating stirring disks, and the rotation speed is adjusted by a variable frequency motor; the modified packing layer is that each stirring section of the multi-stage rotary extraction modified purification column is equipped with special polytetrafluoroethylene modified wire mesh packing; the laminar flow regulating plate utilizes the difference in flow rate of different components in the column to achieve "chromatographic" enrichment and separation of the target product and trace impurities; (3) Gradient elution: using the shear force generated by multi-stage rotation, impurities are enriched in the raffinate and discharged, and the target product enters the extraction phase; the operating temperature of gradient elution is 40℃, the volume ratio of extractant to feed liquid is 1:4, the rotation speed is 200 rpm, the number of gradient stages is 6, and the target product content in the raffinate is ≤0.5% (HPLC method) as the elution endpoint judgment standard.

[0030] (4) Back-extraction and crystallization: After the extract phase is back-extracted with a weak alkaline solution, it is directly crystallized by adjusting the acid. Specifically, the alkaline solution used for back-extraction is a sodium carbonate aqueous solution with a mass fraction of 6%, and the amount used is 0.4 times the volume of the extract phase. The back-extraction temperature is 40℃, and the pH of the aqueous phase after back-extraction is 9. The acid solution used for acid-adjusted crystallization is a hydrochloric acid aqueous solution with a mass fraction of 25%. The pH is adjusted to 3, and the crystallization is carried out at 10℃ for 1.5 h. The target product is obtained by centrifugation, washing, and drying.

[0031] Comparative Example 1: This comparative example describes the preparation of R-(+)-2-(4-hydroxyphenoxy)propionic acid using a traditional activated carbon purification process. The preparation method includes the following steps: (1) Adsorption and decolorization: Add powdered activated carbon (3-5% of the target product mass in the crude D-HPPA solution) to the crude D-HPPA solution, stir and adsorb at 60-70℃ for 30 min, and carry out decolorization treatment; (2) Filtration: While still hot, filter through a plate and frame filter press to remove activated carbon, adsorbed pigments, and some impurities, and collect the filtrate; (3) Acid-adjusted crystallization: Slowly add 20-30% hydrochloric acid aqueous solution to the filtrate to adjust the pH to 2.5-3.5, and cool to 10-15℃ for 2-3 hours to crystallize; if the purity of the product after one crystallization is not up to standard, after filtration, adjust the alkali of the mother liquor again (add 5-10% sodium hydroxide aqueous solution to pH 8.0-9.0) to dissolve, cool to crystallize again, and repeat the above steps 2-3 times; (4) Post-processing: centrifugation, washing with deionized water, and drying to obtain the finished product.

[0032] Example 1: 1000 L of crude D-HPPA solution after the etherification reaction was completed, with an initial chemical purity of 96.2%, was used to prepare R-(+)-2-(4-hydroxyphenoxy)propionic acid using the methods described in Example 3 and Comparative Example 1. The obtained R-(+)-2-(4-hydroxyphenoxy)propionic acid was tested for various indicators, including chemical purity, impurity spectrum, optical purity, appearance, and yield. The content of the target product was quantitatively determined by HPLC. The overall yield was calculated using the following formula: Overall yield (%) = (mass of the target product in the final qualified product ÷ theoretical mass of the target product in the raw material) × 100%.

[0033] (1) Testing items and testing methods

[0034] (2) Test results

[0035] The preparation method of Example 3 of this invention supports continuous operation and does not generate solid waste; it relies on liquid-phase mass transfer for selective separation; and the extractant can be recycled. Yield improvement: After replacing the activated carbon process, physical adsorption losses are reduced, and the overall yield is increased by approximately 1.8%. In contrast, the traditional process in Example 1 is intermittent, the activated carbon cannot be reused, solid waste is generated, and selectivity for structurally similar byproducts is poor; multiple crystallizations result in a large amount of target product remaining in the mother liquor, leading to significant yield loss.

[0036] In summary, the method for preparing R-(+)-2-(4-hydroxyphenoxy)propionic acid described in this invention yields R-(+)-2-(4-hydroxyphenoxy)propionic acid with extremely high purity, achieving a final product purity of 99.8% (national standard is 99.5%), with a significant simultaneous improvement in optical purity. Yield is increased; replacing activated carbon reduces physical adsorption losses, resulting in an overall yield increase of approximately 1.8%. It is green and continuous, with recyclable extractant and no waste carbon generation; the multi-stage rotating column supports continuous operation, increasing production efficiency by 3 times. Precise separation is achieved by utilizing flow rate differences to precisely enrich specific etherification byproducts, especially for the combination of the optimized D-HPPA molecular structure main extractant and co-extraction agent. The internal structural design of the extraction-modified purification column focuses on the combination of "multi-stage rotating disks + PTFE-modified packing material" and its application in the purification of chiral intermediates. Methodology for separation using flow rate differences: Protecting the process of adjusting impurity distribution through physical parameters (rotation speed, flow rate) in a specific extraction device.

Claims

1. A method for preparing R-(+)-2-(4-hydroxyphenoxy)propionic acid, characterized in that, In the preparation of R-(+)-2-(4-hydroxyphenoxy)propionic acid, extraction was performed using R211 extractant. The specific extraction steps are as follows: (1) Preparation of the solution to be treated: After preliminary neutralization, the etherification reaction solution is adjusted to a specific concentration; (2) Continuous extraction: The liquid to be processed enters from the top of the purification column, and the R211 extractant enters countercurrently from the bottom of the column, with the rotation speed controlled at 100-300 rpm; (3) Gradient elution: using the shear force generated by multi-stage rotation, impurities are enriched in the raffinate and discharged, while the target product enters the extraction phase; (4) Back-extraction and crystallization: After the extract phase is back-extracted by a weak alkaline solution, it is directly crystallized by adjusting the acid.

2. The method for preparing R-(+)-2-(4-hydroxyphenoxy)propionic acid as described in claim 1, characterized in that, The preparation of R-(+)-2-(4-hydroxyphenoxy)propionic acid involves using S-2-chloropropionic acid as a raw material, reacting it with sodium hydroxide to form a sodium salt, then reacting it with hydroquinone, and finally extracting it with R211 extractant to obtain R-2-(4-hydroxyphenoxy)propionic acid.

3. The method for preparing R-(+)-2-(4-hydroxyphenoxy)propionic acid as described in claim 1, characterized in that, In step (1), the etherification reaction solution is an aqueous mixture obtained by reacting S-2-chloropropionic acid with hydroquinone after sodium salting. The pH is adjusted to 3.5-4.5, the mass concentration of the aqueous mixture is adjusted to 80-150 g / L, and the temperature is controlled at 40-60℃.

4. The method for preparing R-(+)-2-(4-hydroxyphenoxy)propionic acid as described in claim 1, characterized in that, In step (2), the purification column is a multi-segment rotary extraction modified purification column, and the R211 extractant, by mass percentage, includes 40%~60% main extractant, 10%~20% co-extraction agent, and 20%~40% diluent.

5. The method for preparing R-(+)-2-(4-hydroxyphenoxy)propionic acid as described in claim 4, characterized in that, The multi-stage rotary extraction modification and purification column includes a multi-stage rotor structure, a modified packing layer, and a laminar flow regulating plate.

6. The method for preparing R-(+)-2-(4-hydroxyphenoxy)propionic acid as described in claim 5, characterized in that, The multi-stage rotor structure is that the column body of the multi-segment rotary extraction modification and purification column is equipped with 5-10 independently rotating stirring discs, and the speed is adjusted by a variable frequency motor. The modified packing layer consists of a special polytetrafluoroethylene modified wire mesh packing material placed behind each stirring section of the multi-segment rotary extraction modified purification column. The laminar flow control plate utilizes the difference in flow rate of different components within the column to achieve "chromatographic-grade" enrichment and separation of the target product and trace impurities.

7. The method for preparing R-(+)-2-(4-hydroxyphenoxy)propionic acid as described in claim 4, characterized in that, The main extractant is selected from a modified mixture of methyl isobutyl ketone or tributyl phosphate; the co-extraction aid is a higher fatty alcohol; and the diluent is an alkane or cyclohexane.

8. The method for preparing R-(+)-2-(4-hydroxyphenoxy)propionic acid as described in claim 7, characterized in that, The higher fatty alcohol is octanol.

9. The method for preparing R-(+)-2-(4-hydroxyphenoxy)propionic acid as described in claim 1, characterized in that, In step (3), the gradient elution operation temperature is 30-50℃, the volume ratio of extractant to feed liquid is 1:3-5, the rotation speed is 100-300rpm, the number of gradient segments is 5-10, and the target product content in the raffinate is ≤0.5% as the elution endpoint judgment criterion.

10. The method for preparing R-(+)-2-(4-hydroxyphenoxy)propionic acid as described in claim 1, characterized in that, In step (4), the alkaline solution used for back-extraction is a sodium carbonate aqueous solution with a mass fraction of 3-8%, and the amount used is 0.3-0.5 times the volume of the extract phase. The back-extraction temperature is 35-45℃, and the pH of the aqueous phase after back-extraction is 8.0-9.

5. The acid solution used for acid adjustment and crystallization is a hydrochloric acid aqueous solution with a mass fraction of 20-30%, and the pH is adjusted to 2.5-3.

5. The crystallization is carried out at 5-15℃ for 1-2 hours. The target product is obtained by centrifugation, washing, and drying.

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