阅读说明：本技术 一种r-(+)-2-(4-羟基苯氧基)丙酸的制备方法 (Preparation method of R- (+) -2- (4-hydroxyphenoxy) propionic acid ) 是由 王栋伟 赵宏洋 王诚 刘涛 于 2020-12-30 设计创作，主要内容包括：本发明涉及有机合成技术领域,尤其涉及一种R-(+)-2-(4-羟基苯氧基)丙酸的制备方法。本发明提供的制备方法包括以下步骤：将对硝基苯酚和(S)-(-)-2-氯丙酸在碱性条件下发生取代反应,得到R-(+)-2-(4-硝基苯氧基)丙酸；将所述R-(+)-2-(4-硝基苯氧基)丙酸和H-2在催化剂催化的条件下发生还原反应,得到R-(+)-2-(4-氨基苯氧基)丙酸；将所述R-(+)-2-(4-氨基苯氧基)丙酸与亚硝酸钠在酸性条件下发生重氮化水解反应,得到所述R-(+)-2-(4-羟基苯氧基)丙酸。所述制备方法简单易得,成本低,制备得到的R-(+)-2-(4-羟基苯氧基)丙酸产率高、纯度高。(The invention relates to the technical field of organic synthesis, and particularly relates to a preparation method of R- (+) -2- (4-hydroxyphenoxy) propionic acid. The preparation method provided by the invention comprises the following steps: carrying out substitution reaction on p-nitrophenol and (S) - (-) -2-chloropropionic acid under an alkaline condition to obtain R- (+) -2- (4-nitrophenoxy) propionic acid; reacting the R- (+) -2- (4-nitrophenoxy) propionic acid with H 2 Carrying out reduction reaction under the condition of catalyst catalysis to obtain R- (+) -2- (4-aminophenoxy) propionic acid; carrying out diazotization hydrolysis reaction on the R- (+) -2- (4-aminophenoxy) propionic acid and sodium nitrite under an acidic condition to obtain the R- (+) -2- (4-hydroxyphenoxy) propionic acid. The preparation method is simple and easy to obtain, the cost is low, and the prepared R- (+) -2- (4-hydroxyphenoxy) propionic acid is high in yield and purity.)

1. A preparation method of R- (+) -2- (4-hydroxyphenoxy) propionic acid is characterized by comprising the following steps:

carrying out substitution reaction on p-nitrophenol and (S) - (-) -2-halopropionic acid under alkaline condition to obtain R- (+) -2- (4-nitrophenoxy) propionic acid;

reacting the R- (+) -2- (4-nitrophenoxy) propionic acid with H₂Carrying out reduction reaction under the condition of catalyst catalysis to obtain R- (+) -2- (4-aminophenoxy) propionic acid;

carrying out diazotization hydrolysis reaction on the R- (+) -2- (4-aminophenoxy) propionic acid and sodium nitrite under an acidic condition to obtain the R- (+) -2- (4-hydroxyphenoxy) propionic acid.

2. The process according to claim 1, wherein the molar ratio of p-nitrophenol to (S) - (-) -2-halopropionic acid is 1 (1 to 1.2).

3. The method of claim 1, wherein the alkaline conditions are provided by a soluble base solution;

the pH value under the alkaline condition is 12-14.

4. The method of claim 1, 2 or 3, wherein the temperature of the substitution reaction is 65 to 80 ℃.

5. The method of claim 1, wherein the catalyst is a palladium on carbon catalyst;

the mass ratio of the palladium carbon catalyst to the R- (+) -2- (4-nitrophenoxy) propionic acid is (0.5-1): 100.

6. the method according to claim 1 or 5, wherein the temperature of the reduction reaction is 55 to 65 ℃;

the time for stopping the reduction reaction is determined by detecting the area normalized content of the R- (+) -2- (4-nitrophenoxy) propionic acid in the reaction liquid by liquid chromatography, wherein the normalized content is less than 0.5%.

7. The method according to claim 1, wherein the acidic condition is provided by concentrated sulfuric acid having a mass concentration of 50%;

the pH value under the acidic condition is 0-1, and the pH value is not equal to 0.

8. The method according to claim 1 or 7, wherein the molar ratio of the sodium nitrite to the R- (+) -2- (4-aminophenoxy) propionic acid is (1 to 1.2): 1.

9. the preparation method according to claim 8, wherein the temperature of the diazotization hydrolysis reaction is 0-10 ℃;

the time for stopping the diazotization hydrolysis reaction is subject to the detection of the area normalized content of the R- (+) -2- (4-aminophenoxy) propionic acid in the reaction liquid by liquid chromatography, which is less than 0.5%.

10. The process of claim 1, wherein the (S) - (-) -2-halopropionic acid is replaced with (S) - (-) -2-halopropionic acid ester.

Technical Field

The invention relates to the technical field of organic synthesis, and particularly relates to a preparation method of R- (+) -2- (4-hydroxyphenoxy) propionic acid.

Background

The aryloxy propionic acid herbicide is a novel herbicide with optical activity, and has the characteristics of high efficiency, low toxicity, weeding spectrum, high selectivity, easy biodegradation, long application period, safety to crops and the like. Wherein R- (+) -2- (4-hydroxyphenoxy) propionic acid (DHPPA) is an important intermediate for synthesizing dozens of aryloxy propionic acid herbicides such as thiazole diclofop-methyl, haloxyfop-p-ethyl, quizalofop-p-ethyl, clodinafop-propargyl, Biaoma, high-efficiency galin, cyhalofop-butyl and the like, so the synthesis of DHPPA has important significance. The current DHPPA synthesis method comprises the following steps:

1) hydroquinone is used as a raw material to react with 2-methyl chloropropionate to obtain a racemate, and the racemate is resolved to obtain DHPPA, the method has low yield and high raw material cost, and the reaction equation is shown as formula 1:

2) european patent EP0180126 discloses L-methyl lactate and paratoluensulfonyl chloride are synthesized into L-methyl tosylate, and then the L-methyl tosylate reacts with hydroquinone to obtain DHPPA through configuration inversion in the reaction process, the product obtained by the method has poor optical purity, the e.e value is only 90-95%, and the byproduct p-toluenesulfonic acid is difficult to recover in wastewater, so that the environmental pollution is large, and the reaction equation is shown as formula 2:

3) US patent No. 4489207 discloses a one-step process for synthesizing DHPPA by reacting hydroquinone with (S) - (-) -2-chloropropionic acid, which produces a large amount of waste water in an alkaline aqueous solution, and DHPPA has a certain solubility in water, and a part of the product is not recovered when dissolved in water, so that the yield is low, and the reaction equation is as shown in formula 3:

as can be seen from the above, the method uses hydroquinone as a raw material, inevitably generates hydroquinone disubstituted impurities (the structural formula is shown as formula 4, and the content accounts for 10-20%), so that the product is difficult to purify, and the product quality cannot be ensured;

disclosure of Invention

The invention aims to provide a preparation method of R- (+) -2- (4-hydroxyphenoxy) propionic acid, and the R- (+) -2- (4-hydroxyphenoxy) propionic acid prepared by the preparation method has high yield and high purity.

In order to achieve the above object, the present invention provides the following technical solutions:

the invention provides a preparation method of R- (+) -2- (4-hydroxyphenoxy) propionic acid, which comprises the following steps:

carrying out substitution reaction on p-nitrophenol and (S) - (-) -2-halopropionic acid under alkaline condition to obtain R- (+) -2- (4-nitrophenoxy) propionic acid;

reacting the R- (+) -2- (4-nitrophenoxy) propionic acid with H₂Carrying out reduction reaction under the condition of catalyst catalysis to obtain R- (+) -2- (4-aminophenoxy) propionic acid;

carrying out diazotization hydrolysis reaction on the R- (+) -2- (4-aminophenoxy) propionic acid and sodium nitrite under an acidic condition to obtain the R- (+) -2- (4-hydroxyphenoxy) propionic acid.

Preferably, the molar ratio of the p-nitrophenol to the (S) - (-) -2-chloropropionic acid is 1 (1-1.2).

Preferably, the alkaline conditions are provided by a soluble alkali solution;

the pH value under the alkaline condition is 12-14.

Preferably, the temperature of the substitution reaction is 65-80 ℃.

Preferably, the catalyst is a palladium on carbon catalyst;

the mass ratio of the palladium carbon catalyst to the R- (+) -2- (4-nitrophenoxy) propionic acid is (0.5-1): 100.

preferably, the temperature of the reduction reaction is 55-65 ℃;

the time for stopping the reduction reaction is determined by detecting the area normalized content of the R- (+) -2- (4-nitrophenoxy) propionic acid in the reaction liquid by liquid chromatography, wherein the normalized content is less than 0.5%.

Preferably, the acidic condition is provided by concentrated sulfuric acid with the mass concentration of 50%;

the pH value under the acidic condition is 0-1, and the pH value is not equal to 0.

Preferably, the molar ratio of the sodium nitrite to the R- (+) -2- (4-aminophenoxy) propionic acid is (1-1.2): 1.

preferably, the temperature of the diazotization hydrolysis reaction is 0-10 ℃;

the time for stopping the diazotization hydrolysis reaction is subject to the detection of the area normalized content of the R- (+) -2- (4-aminophenoxy) propionic acid in the reaction liquid by liquid chromatography, which is less than 0.5%.

Preferably, the (S) - (-) -2-halopropionic acid is replaced with (S) - (-) -2-halopropionate.

The invention provides a preparation method of R- (+) -2- (4-hydroxyphenoxy) propionic acid, which comprises the following steps: carrying out substitution reaction on p-nitrophenol and (S) - (-) -2-chloropropionic acid under an alkaline condition to obtain R- (+) -2- (4-nitrophenoxy) propionic acid; reacting the R- (+) -2- (4-nitrophenoxy) propionic acid with H₂Carrying out reduction reaction under the condition of catalyst catalysis to obtain R- (+) -2- (4-aminophenoxy) propionic acid; carrying out diazotization hydrolysis reaction on the R- (+) -2- (4-aminophenoxy) propionic acid and sodium nitrite under an acidic condition to obtain the R- (+) -2- (4-hydroxyphenoxy) propionic acid. The preparation method is simple and easy to obtain, the operation of the working procedures is simple, hydroquinone is avoided being used as a raw material, and the problems of low raw material utilization rate, low product quality and the like caused by the double-substituted impurity of hydroquinone generated in the reaction due to high cost of the hydroquinone used as the raw material in the traditional method are solved.

Detailed Description

The invention provides a preparation method of R- (+) -2- (4-hydroxyphenoxy) propionic acid, which comprises the following steps:

carrying out substitution reaction on p-nitrophenol and (S) - (-) -2-halopropionic acid under alkaline condition to obtain R- (+) -2- (4-nitrophenoxy) propionic acid;

reacting the R- (+) -2- (4-nitrophenoxy) propionic acid with H₂Carrying out reduction reaction under the condition of catalyst catalysis to obtain R- (+) -2- (4-aminophenoxy) propionic acid;

carrying out diazotization hydrolysis reaction on the R- (+) -2- (4-aminophenoxy) propionic acid and sodium nitrite under an acidic condition to obtain the R- (+) -2- (4-hydroxyphenoxy) propionic acid.

In the present invention, all the starting materials for the preparation are commercially available products well known to those skilled in the art unless otherwise specified.

The invention carries out substitution reaction on p-nitrophenol and (S) - (-) -2-halopropionic acid under the alkaline condition to obtain R- (+) -2- (4-nitrophenoxy) propionic acid.

In the invention, the molar ratio of the p-nitrophenol to the (S) - (-) -2-halopropionic acid is preferably 1 (1-1.2), and more preferably 1:1.

In the present invention, the (S) - (-) -2-halopropionic acid is preferably (S) - (-) -2-chloropropionic acid or (S) - (-) -2-bromopropionic acid.

In the present invention, the pH value of the alkaline condition is preferably 12 to 14, and more preferably 13. The alkaline conditions are preferably provided by a soluble alkali solution, the soluble alkali in the soluble alkali solution preferably comprising a soluble inorganic alkali or a soluble organic alkali; the soluble inorganic base is preferably sodium hydroxide, potassium hydroxide or potassium carbonate; the soluble organic base is preferably sodium methoxide, sodium ethoxide or potassium tert-butoxide. In the invention, the molar ratio of the alkali to the p-nitrophenol in the soluble alkali solution is preferably (0.5-2.5): 1. in a specific embodiment of the present invention, the alkaline condition is a sodium hydroxide aqueous solution with a mass concentration of 25-35%.

In the present invention, the process of the substitution reaction is preferably carried out by mixing p-nitrophenol and a soluble alkali solution, heating to the temperature at which the substitution reaction occurs, and then adding dropwise (S) - (-) -2-halopropionic acid. The present invention does not limit the mixing in any particular way, and the mixing may be carried out by a process known to those skilled in the art. In the invention, the temperature of the substitution reaction is preferably 65-80 ℃, and more preferably 70-75 ℃. In the invention, after the temperature is raised to the temperature of the substitution reaction, the method also preferably comprises the step of continuously stirring for 25-35 min, more preferably continuously stirring for 30 min; the stirring rate is not particularly limited in the present invention, and may be a rate well known to those skilled in the art. The dropping process of the (S) - (-) -2-halopropionic acid is not particularly limited in the present invention, and may be carried out by a process known to those skilled in the art. In the present invention, the substitution reaction starts when the (S) - (-) -2-halopropionic acid is dropped.

After the dropwise adding is completed, the method also preferably comprises the step of continuously reacting for 1-5 hours to ensure that the p-nitrophenol is fully reacted, and more preferably continuously reacting for 2-3 hours.

In the present invention, the (S) - (-) -2-halopropionic acid is preferably replaced with (S) - (-) -2-halopropionate; the (S) - (-) -2-halopropionate is preferably methyl (S) - (-) -2-chloropropionate, ethyl (S) - (-) -2-chloropropionate, methyl (S) - (-) -2-bromopropionate or ethyl (S) - (-) -2-bromopropionate; the amount of the (S) - (-) -2-halopropionate is preferably referred to the amount of the (S) - (-) -2-halopropionic acid.

After the substitution reaction is completed, the invention also preferably comprises the steps of adjusting the pH value and filtering of the product system obtained in sequence. The pH value is preferably adjusted by adopting concentrated hydrochloric acid; the concentration of the concentrated hydrochloric acid is preferably 32-36%. The pH value after adjustment is preferably 1-2. The filtration is not particularly limited in the present invention and may be carried out by a process known to those skilled in the art.

In the invention, when the reaction raw material is (S) - (-) -2-halopropionic acid, the reaction formula of the substitution reaction is shown as formula 5:

when the reaction raw material is (S) - (-) -2-halopropionate, the substitution reaction is carried out under alkaline conditions, and the ester group in the substitution reaction can be further hydrolyzed and converted into carboxyl, namely, the same product is obtained as that obtained by the technical scheme that the reaction raw material is (S) - (-) -2-halopropionic acid.

After R- (+) -2- (4-nitrophenoxy) propionic acid is obtained, the invention combines the R- (+) -2- (4-nitrophenoxy) propionic acid and H₂Carrying out reduction reaction under the condition of catalyst catalysis to obtain R- (+) -2- (4-aminophenoxy) propionic acid.

In the present invention, the catalyst can preferably be a palladium on carbon catalyst; the mass ratio of the palladium carbon catalyst to the R- (+) -2- (4-nitrophenoxy) propionic acid is preferably (0.5-1.0): 100, more preferably 0.86: 100.

In the invention, the temperature of the reduction reaction is preferably 55-65 ℃, and more preferably 60 ℃.

In the present invention, the reduction reaction is preferably carried out in a methanol medium.

In the present invention, the reduction reaction is preferably performed by mixing the R- (+) -2- (4-nitrophenoxy) propionic acid, methanol and palladium on carbon catalyst, heating, and introducing hydrogen gas. In the invention, the dosage ratio of the R- (+) -2- (4-nitrophenoxy) propionic acid to the methanol is preferably 1g (1-2) mL, and more preferably 1g:1.5 mL. In the present invention, the target temperature for the temperature increase is preferably the temperature of the reduction reaction. In the invention, the introducing speed of the hydrogen is preferably 1-3 bubbles per second, more preferably 2 bubbles per second, and the inner diameter of the vent pipe for introducing the hydrogen is preferably 8 mm.

In the present invention, the time for stopping the reduction reaction is preferably based on the detection of an area normalized content of the R- (+) -2- (4-nitrophenoxy) propionic acid in the reaction solution by liquid chromatography < 0.5%.

After the reduction is finished, the method also preferably comprises the steps of sequentially cooling to 20-25 ℃, filtering and concentrating under reduced pressure. The filtration is not particularly limited in the present invention and may be carried out by a process known to those skilled in the art. In the present invention, the solid obtained by the filtration is used for recovering the palladium-carbon catalyst; the filtrate obtained by filtration is used for subsequent decompression concentration; the concentration under reduced pressure in the present invention is not particularly limited, and may be carried out by a method known to those skilled in the art.

In the present invention, the process of the reduction reaction is shown in formula 6:

after the R- (+) -2- (4-aminophenoxy) propionic acid is obtained, the R- (+) -2- (4-aminophenoxy) propionic acid and sodium nitrite are subjected to diazotization hydrolysis reaction under an acidic condition to obtain the R- (+) -2- (4-hydroxyphenoxy) propionic acid.

In the present invention, the molar ratio of R- (+) -2- (4-aminophenoxy) propionic acid to sodium nitrite is preferably 1: (1-1.2), more preferably 1: 1.1. In the invention, the pH value of the acidic condition is preferably 0-1, and the pH is not equal to 0, and more preferably 0.5; in the present invention, the acidic condition is preferably provided by concentrated sulfuric acid having a mass concentration of 50%. The dosage of the concentrated hydrochloric acid is not limited in any way, and the dosage well known to those skilled in the art can ensure that the acidic condition is within the range of 0-1 of pH value.

In the invention, the temperature of the diazotization hydrolysis reaction is preferably 0-10 ℃, and more preferably 3-6 ℃.

In the present invention, the procedure of the diazotization hydrolysis reaction is preferably as follows: mixing sodium nitrite with water to obtain a sodium nitrite aqueous solution; and (2) mixing the R- (+) -2- (4-aminophenoxy) propionic acid with concentrated sulfuric acid with the mass concentration of 50%, and then dropwise adding the sodium nitrite aqueous solution. In the present invention, the mass concentration of the sodium nitrite aqueous solution is preferably 20 to 30%, and more preferably 35%. In the present invention, the mixing of the R- (+) -2- (4-aminophenoxy) propionic acid with concentrated sulfuric acid having a mass concentration of 50% is preferably performed under stirring; the stirring is not particularly limited in the present invention, and may be carried out by a procedure well known to those skilled in the art. The dropping process is not particularly limited, and may be carried out by a process known to those skilled in the art. In the invention, the beginning of the dropwise addition of the sodium nitrite aqueous solution is the beginning of the diazotization hydrolysis reaction.

In the invention, the time for stopping the diazotization hydrolysis reaction is determined by detecting the area normalized content of the R- (+) -2- (4-aminophenoxy) propionic acid in the reaction liquid by liquid chromatography, wherein the area normalized content is less than 0.5%.

After the diazotization hydrolysis reaction is finished, the method also preferably comprises the steps of sequentially adding urea, heating for hydrolysis, cooling, first filtering, recrystallization, second filtering and drying. In the invention, the purpose of adding urea is to remove sodium nitrite which is not completely reacted in the reaction; the adding amount of the urea is not limited in any way, and the sodium nitrite which is not completely reacted can be completely removed. In the present invention, the temperature of the heated hydrolysis is preferably 60 ℃; the first filtration and the second filtration are not particularly limited in the present invention, and may be performed by a process known to those skilled in the art. The process of cooling is not limited in any way, and the process known by the technical personnel in the field can ensure that crystals are precipitated; in the invention, the solvent used for recrystallization is preferably water; the recrystallization process is not particularly limited in the present invention, and may be performed by a process known to those skilled in the art. In the present invention, the drying mode is preferably drying, and the drying is not particularly limited in the present invention, and may be performed by a process well known to those skilled in the art.

In the present invention, the process of the diazotization hydrolysis reaction is shown as formula 7:

the preparation method of R- (+) -2- (4-hydroxyphenoxy) propionic acid provided by the present invention is described in detail with reference to the following examples, but they should not be construed as limiting the scope of the present invention.

Example 1

(1) Mixing 139.1g (1mol) of p-nitrophenol with 200mL of 30% sodium hydroxide aqueous solution, heating to 70 ℃, stirring for 30min (pH is 13), dropwise adding 108.5g of (S) - (-) -2-chloropropionic acid, keeping the temperature at 70 ℃ for 2h, adjusting the pH value to 1.5 by using 32% concentrated hydrochloric acid, filtering and drying to obtain 191.2g of light yellow solid R- (+) -2- (4-nitrophenoxy) propionic acid, wherein the HPLC area normalized content is 98.1%; the yield is 90.5%;

(2) mixing 191.2gR- (+) -2- (4-nitrophenoxy) propionic acid, 300mL of methanol and 1.2g of palladium carbon catalyst, heating to 60 ℃, introducing hydrogen at a rate of 2 bubbles per second (the inner diameter of a hydrogen tube is 8mm), stopping introducing the hydrogen when the area normalized content of the R- (+) -2- (4-nitrophenoxy) propionic acid is detected to be less than 0.5% by liquid chromatography, cooling to 25 ℃, filtering and recovering the palladium carbon catalyst, and concentrating the filtrate under reduced pressure to obtain 160.3g R- (+) -2- (4-aminophenoxy) propionic acid, wherein the HPLC area normalized content is 98.5%, and the yield is 97.7%;

(3) mixing and stirring 160.3g R- (+) -2- (4-aminophenoxy) propionic acid and 340g of concentrated sulfuric acid with the mass concentration of 50%, cooling to 3 ℃, dropwise adding 66.5g of sodium nitrite and 266g of water to obtain a sodium nitrite solution, continuing diazotization hydrolysis reaction after dropwise adding, stopping the reaction when the area normalized content of the R- (+) -2- (4-aminophenoxy) propionic acid in the reaction solution is less than 0.5% by liquid chromatography, counting 2g of urea to remove the sodium nitrite which does not participate in the reaction, heating to 60 ℃ for hydrolysis, cooling to separate out crystals, filtering to obtain 160.3g of white solid, wherein the HPLC area normalized content is 97.6%; adding water for recrystallization, filtering and drying to obtain 132.8g of white solid R- (+) -2- (4-hydroxyphenoxy) propionic acid; the total yield of the R- (+) -2- (4-hydroxyphenoxy) propionic acid is 72.9 percent;

performing nuclear magnetic test on the R- (+) -2- (4-hydroxyphenoxy) propionic acid, wherein the test result is as follows: 1H NMR (400MHz, CDCl)₃)，δ＝1.51(s，3H，CH₃)，4.58(q，1H，CH)，6.81(m，2H，ArH)，7.02(m，2H，ArH)，12.01(s，1H，OH)；

Mass spectrometric detection of MS (ESI), M/z 183.2[ M ]⁺H]⁺；

Performing liquid chromatography detection on the prepared R- (+) -2- (4-hydroxyphenoxy) propionic acid under the following detection conditions: dissolving the sample with acetonitrile, performing Shimadzu liquid chromatograph C18 chromatographic column with the wavelength of 230 column temperature and the mobile phase acetonitrile of 30 ℃: 15:85 of water; the measured HPLC area normalized content is 99.7%;

performing chiral test on the prepared R- (+) -2- (4-hydroxyphenoxy) propionic acid by using a liquid chromatography chiral column, wherein the detection conditions comprise that: chromatographic column chromatography Chiralcel OB-H,0.4cm (i.d). times.25 cm; mobile phase: volume ratio of heptane to isopropanol 85:15, analysis conditions: the flow rate is 1mL/min, the column temperature is 25 ℃, the wavelength is 230nm, the obtained final product is measured to be R- (+) -2- (4-hydroxyphenoxy) propionic acid, and the optical purity e.e is more than 99.0%.

Example 2

Mixing 139.1g of p-nitrophenol with 200mL of 35% sodium hydroxide aqueous solution, heating to 75 ℃, stirring for 30min (pH is 13), dropwise adding 108.5g of (S) - (-) -2-chloropropionic acid, keeping the temperature at 75 ℃ for 2h, adjusting the pH value to 1.2 by using 34% concentrated hydrochloric acid, filtering and drying to obtain 192.4g of pale yellow solid R- (+) -2- (4-nitrophenoxy) propionic acid, wherein the HPLC area normalized content is 98.2%, and the yield is 90.9%;

mixing 192.4gR- (+) -2- (4-nitrophenoxy) propionic acid, 300mL methanol and 1.2g palladium carbon catalyst, heating to 55 ℃, introducing hydrogen at a rate of 2 bubbles per second, stopping introducing hydrogen when the area normalized content of R- (+) -2- (4-nitrophenoxy) propionic acid detected by liquid chromatography is less than 0.5%, cooling to 25 ℃, filtering and recovering the palladium carbon catalyst, and concentrating the filtrate under reduced pressure to obtain 159.7g R- (+) -2- (4-aminophenoxy) propionic acid, wherein the HPLC area normalized content is 98.3%, and the yield is 96.9%;

mixing and stirring 168.7g R- (+) -2- (4-aminophenoxy) propionic acid and 340g of concentrated sulfuric acid with the mass concentration of 50%, cooling to 5 ℃, dropwise adding 66.5g of sodium nitrite and 266g of water to obtain a sodium nitrite solution, continuing diazotization hydrolysis reaction after dropwise adding, stopping the reaction when the area normalized content of the R- (+) -2- (4-aminophenoxy) propionic acid in the reaction solution is less than 0.5% by liquid chromatography, counting 2g of urea to remove the sodium nitrite which does not participate in the reaction, heating to 60 ℃ for hydrolysis, cooling to separate out crystals, filtering to obtain 162.60g of white solid, wherein the HPLC area normalized content is 97.5%; adding water for recrystallization, filtering and drying to obtain 131.6g of white solid R- (+) -2- (4-hydroxyphenoxy) propionic acid; the total yield of the R- (+) -2- (4-hydroxyphenoxy) propionic acid is 72.2%, the HPLC area normalized content is 99.7%, and the optical purity e.e is more than 99.0%.

The R- (+) -2- (4-hydroxyphenoxy) propionic acid was subjected to a nuclear magnetic test, and the test results were similar to those of example 1.

Example 3

Mixing 139.1g (1mol) of p-nitrophenol with 200mL of 25% aqueous sodium hydroxide solution, heating to 80 ℃, stirring for 30min (pH is 12), dropwise adding 108.5g of (S) - (-) -2-chloropropionic acid, keeping the temperature at 80 ℃ for 2h, adjusting the pH value to 1.41 by using 36% concentrated hydrochloric acid, and filtering to obtain 189.6g of light yellow solid R- (+) -2- (4-nitrophenoxy) propionic acid, wherein the HPLC area normalized content is 98.2%, and the yield is 89.8%;

mixing 189.6gR- (+) -2- (4-nitrophenoxy) propionic acid, 300mL methanol and 1.5g palladium carbon catalyst, heating to 60 ℃, introducing hydrogen at a rate of 2 bubbles per second, stopping introducing hydrogen when the mass area normalized content of the R- (+) -2- (4-nitrophenoxy) propionic acid detected by liquid chromatography is less than 0.5%, cooling to 25 ℃, filtering and recovering the palladium carbon catalyst, and concentrating the filtrate under reduced pressure to obtain 159.6g R- (+) -2- (4-aminophenoxy) propionic acid, wherein the HPLC area normalized content is 98.6%, and the yield is 98.1%;

mixing and stirring 159.6g R- (+) -2- (4-aminophenoxy) propionic acid and 340g of concentrated sulfuric acid with the mass concentration of 50%, cooling to 3 ℃, dropwise adding 70.5g of sodium nitrite and 266g of water to obtain a sodium nitrite solution, continuing diazotization hydrolysis reaction after dropwise adding, stopping the reaction when the area normalized content of the R- (+) -2- (4-aminophenoxy) propionic acid in the reaction solution is less than 0.5% by liquid chromatography, counting 2g of urea to remove the sodium nitrite which does not participate in the reaction, heating to 60 ℃ for hydrolysis, cooling to separate out crystals, filtering to obtain 160.9g of white solid, wherein the HPLC area normalized content is 97.6%; adding water for recrystallization, filtering and drying to obtain 130.1g of white solid R- (+) -2- (4-hydroxyphenoxy) propionic acid; the total yield of the R- (+) -2- (4-hydroxyphenoxy) propionic acid is 71.4%, the HPLC area normalized content is 99.5%, and the optical purity e.e is more than 99.0%.

The R- (+) -2- (4-hydroxyphenoxy) propionic acid was subjected to a nuclear magnetic test, and the test results were similar to those of example 1.

Comparative example 1

20.8g of sodium hydroxide solid and 55.6g of hydroquinone are added into a 1L four-neck flask, 300g of water is added, stirring is carried out under the protection of nitrogen until the solid is completely dissolved, 22.4g of (S) - (-) -2-chloropropionic acid is added, the temperature is raised to 70 ℃ for reaction for 3 hours, the liquid phase detection is carried out, the reaction is stopped when the (S) - (-) -2-chloropropionic acid as a raw material is completely reacted, the pH of a hydrochloric acid adjusting system is 6, MIBK is used for extraction for three times, the pH of an aqueous layer is adjusted to 1 by hydrochloric acid, and the R- (+) -2- (4-hydroxyphenoxy) propionic acid is obtained by filtering and purification, wherein the yield is 40 percent, which indicates that a large amount of disubstituted impurities are formed in the.

The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.