Synthesis method of 2, 4, 5-trifluorophenylacetic acid

Abstract

The invention discloses a synthesis method of 2, 4, 5-trifluorophenylacetic acid, which comprises the following steps: by taking cheap and easily available o-chloronitrobenzene as a raw material, reacting with sodium nitrate in a sulfuric acid and trifluoroacetic acid system, separating generated 2, 4-dinitrochlorobenzene through melt crystallization, and continuing to synthesize 2, 4-dinitrochlorobenzene in methyl chloroacetate to obtain 2, 4, 5-trifluorophenylacetic acid. The method comprises the following steps: carrying out indirect aromatic nucleophilic substitution reaction on 2, 4-dinitrophenylacetic acid under the condition of sodium hydride to generate 5-chloro-2, 4-dinitrophenylacetic acid methyl ester, separating, carrying out fluorination reaction on the 5-chloro-2, 4-dinitrophenylacetic acid methyl ester and potassium fluoride under the action of a phase transfer catalyst, carrying out rectification separation to obtain 2, 4, 5-trifluorophenylacetic acid, and carrying out hydrolytic acidification on the 2, 4, 5-trifluorophenylacetic acid in a sodium hydroxide aqueous solution to obtain 2, 4, 5-trifluorophenylacetic acid. And the process route is safer, more environment-friendly, more efficient and lower in cost.

Description

Technical Field

[0001] This invention relates to the field of 2,4,5-trifluorophenylacetic acid production technology, and specifically to a method for synthesizing 2,4,5-trifluorophenylacetic acid. Background Technology

[0002] 2,4,5-Trifluorophenylacetic acid is an important intermediate in the synthesis of sitagliptin, the first dipeptidyl peptidase (DPP)-IV inhibitor for diabetes developed by Merck in the United States. It was launched in 2006 and is primarily used to treat non-insulin-dependent (type II) diabetes. Its unique mechanism of action, good efficacy, and low risk of hypoglycemia make it one of the most promising antidiabetic drugs for clinical application.

[0003] Chinese patent CN101659611A discloses a method for synthesizing 2,4,5-trifluorophenylacetic acid, which involves reacting 1,2,4-trifluorobenzene with paraformaldehyde and a chlorinating agent to obtain 2,4,5-trifluorobenzyl chloride, which is then reacted with a cyaniding reagent to obtain 2,4,5-trifluorophenylacetonitrile, and hydrolyzed under acidic or alkaline conditions to obtain 2,4,5-trifluorophenylacetic acid. Chinese patent CN102690166A discloses a method for chloromethylating 1,2,4-trifluorobenzene and paraformaldehyde with sulfuric acid purged with hydrogen chloride gas as a chlorinating agent to obtain 2,4,5-trifluorobenzyl chloride, followed by hydrogenation in a sodium cyanide, water, and acetic acid system to obtain phenylacetonitrile, and hydrolysis to obtain 2,4,5-trifluorophenylacetic acid. All of the above routes use 1,2,4-trifluorobenzene as raw material, but synthesizing 1,2,4-trifluorobenzene is quite difficult. Conventional routes require multiple high-risk processes such as fluorination, nitration, or diazotization.

[0004] Chinese patent CN110498730A discloses a method for synthesizing 1,2,4-trifluorobenzene. Using 2,4-dichlorofluorobenzene as a raw material, nitration is performed in a nitric acid and sulfuric acid system to generate 2,4-dichloro5-fluoronitrobenzene. This is then fluorinated with potassium fluoride under a phase transfer catalyst to obtain 2,4,5-trifluoronitrobenzene, followed by catalytic hydrogenation to obtain 2,4,5-trifluoroaniline, which is then reduced by diazo to obtain 1,2,4-trifluorobenzene. The literature "Improved Synthesis Process of Key Intermediates 2,4,5-Trifluorophenylacetic Acid and Fluoroquinones of Sitagliptin" (Zhejiang University of Technology, Xu Panyun) introduces two methods for synthesizing 2,4,5-trifluorophenylacetic acid using 1,2,4-trifluorobenzene as an intermediate. Method 1 involves using m-dichlorobenzene as a raw material, followed by nitration, fluorination, hydrogenation reduction, and the Heimer reaction to prepare 1,2,4-trifluorobenzene. Then, using 1,2,4-trifluorobenzene as a raw material, 2,4,5-trifluorophenylacetic acid is prepared via chloromethylation and a Grignard reaction. Method 2 involves using 2,4-dichlorofluorobenzene as a raw material, followed by nitration, fluorination, hydrogenation reduction, and diazotization deamination to prepare 1,2,4-trifluorobenzene. Then, using 1,2,4-trifluorobenzene as a raw material, 2,4,5-trifluorophenylacetic acid is prepared via chloromethylation and a Grignard reaction. The main disadvantages of the above process are: 1. The overall route involves many steps, a long process, low yield, and high equipment investment; 2. The route using 2,4-dichloronitrobenzene as the initial raw material requires multiple fluorination processes with low yield and high risk; 3. The reaction involves nitration under elevated temperature conditions, using a mixed acid system of nitric acid and sulfuric acid. The nitration process is exothermic, with large heat fluctuations, high risk, and generates a large amount of waste acid, resulting in high treatment costs; 4. The route involves a diazotization reaction, and the resulting diazonium salt is unstable, posing certain safety risks. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to provide a method for synthesizing 2,4,5-trifluorophenylacetic acid, which has high yield and purity and good safety, in order to address the shortcomings of the existing technology.

[0006] To solve the above-mentioned technical problems, the technical solution of the present invention is as follows:

[0007] A method for synthesizing 2,4,5-trifluorophenylacetic acid, characterized by comprising the following steps:

[0008] S1: Add o-chloronitrobenzene and trifluoroacetic acid to the reactor, stir to dissolve, and then add sodium nitrate and concentrated sulfuric acid. React at 25°C for 8-12 hours. Add the reaction liquid dropwise to water, heat to 50°C, separate the organic phase, and obtain 2,4-dinitrochlorobenzene.

[0009] S2: 2,4-Dinitrochlorobenzene was added to the reaction vessel, followed by dimethyl sulfoxide. Methyl chloroacetate was added dropwise with stirring. Sodium hydride was added in portions (5 portions over 30 min) under nitrogen protection. The reaction was carried out at 25°C for 12 h. The reaction mixture was poured into ice water with stirring and extracted with ethyl acetate to obtain methyl 5-chloro-2,4-dinitrophenylacetate.

[0010] S3: 5-chloro-2,4-dinitrophenylacetic acid methyl ester was added to the reactor, followed by sulfolane. While stirring, potassium fluoride, phthaloyl chloride and tetramethylammonium chloride were added. The temperature was raised to 140-160℃ and reacted for 8-10 hours. After the reaction was completed, the temperature was lowered to room temperature. The aqueous phase was separated by washing with water, and the oil phase was separated by distillation to obtain 2,4,5-trifluorophenylacetic acid methyl ester.

[0011] S4: Methyl 2,4,5-trifluorophenylacetic acid was added to an aqueous sodium hydroxide solution and hydrolyzed at 60°C for 4 hours. After cooling to room temperature, the pH was adjusted to 2, and the mixture was filtered, washed with water, and dried to obtain 2,4,5-trifluorophenylacetic acid.

[0012] The specific process route is as follows:

[0013]

[0014] Preferably, in step S1, the mass ratio of o-chloronitrobenzene to trifluoroacetic acid is 1:6, and the molar ratio of o-chloronitrobenzene, sodium nitrate, and concentrated sulfuric acid is 1:3 to 5:3 to 5.

[0015] Preferably, the organic phase obtained in step S1 is placed in a crystallizer and cooled to 15°C for 3 hours, then heated to 30°C within 3 hours. The resulting crystals are purified 2,4-dinitrochlorobenzene, used in the reaction in step S2. The specific purification steps are as follows: the organic phase is placed in a crystallizer, and the material is first heated to 50°C using a high-low temperature integrated machine to completely melt the material. Then, a linear cooling program is set to cool the material to 30°C, with a total cooling temperature of 20°C, taking 120 minutes. Subsequently, a crystal growth process is performed to obtain crystals in the crystallizer. After the crystallization and cooling process is completed, a linear cooling program is set to lower the temperature to 15°C, for a total cooling of 15°C over 60 minutes. Then, the crystallization process is carried out to purify the material. After the crystallization cooling program is completed, the temperature is maintained at this level for 30 minutes. After the maintenance is completed, the residue is discharged, and the low-concentration liquid is released from the crystallizer. Then, the temperature is raised to 20°C through a linear program over 60 minutes. Finally, the sweating operation is performed, and the temperature is raised to 30°C through a linear program over 120 minutes, finally obtaining purified crystals.

[0016] Preferably, the residual liquid and sweat discharged from the bottom of the crystallizer during the crystallization process are collected, and 2,4-dinitrochlorobenzene is recovered after crystallization and separation.

[0017] In step S2, the mass ratio of 2,4-dinitrochlorobenzene to dimethyl sulfoxide is 1:2.

[0018] In step S2, the molar ratio of 2,4-dinitrochlorobenzene, methyl chloroacetate, and sodium hydride is 1:1.0 to 1.2:1.4, wherein the sodium hydride is used in the form of a 60 wt% oil dispersion (i.e., 60% w / w sodium hydride dispersed in mineral oil).

[0019] In step S2, the reaction solution is extracted with ethyl acetate, washed with saturated brine 1-3 times, dried with anhydrous sodium sulfate, filtered, and the ethyl acetate is removed by vacuum distillation to obtain methyl 5-chloro-2,4-dinitrophenylacetate.

[0020] Before adding potassium fluoride in step S3, the stirring speed is controlled at 150 rpm. After adding potassium fluoride, the speed is increased to 200 rpm. After the temperature reaches the reaction temperature, the speed is increased to 300 rpm. After reacting for 3 hours, the speed is increased to 500 rpm until the reaction is complete.

[0021] In step S3, the mass ratio of methyl 5-chloro-2,4-dinitrophenylacetate, sulfolane, and tetramethylammonium chloride is 1:2:0.03.

[0022] In step S3, the molar ratio of methyl 5-chloro-2,4-dinitrophenylacetate, potassium fluoride, and phthaloyl chloride is 1:3.3-3.7:2.

[0023] In step S4, the molar ratio of methyl 2,4,5-trifluorophenylacetate to sodium hydroxide is 1:1.2, and the concentration of the sodium hydroxide aqueous solution is 10-15 wt%.

[0024] Due to the adoption of the above technical solution, the beneficial effects of the present invention are:

[0025] 1. This invention uses sodium nitrate as the nitrate source for room temperature nitration, which reduces the amount of sulfuric acid used, avoids the use of nitric acid, and significantly lowers the nitration temperature, thus improving the safety of the reaction.

[0026] 2. This invention fluorinates three positions at a time. Compared with the fluorinated substrate of the original process, the fluorinated substrate of this invention has increased activity for aromatic nucleophilic substitution due to the electron-withdrawing effect of the two nitro groups on the benzene ring. The fluorination reaction conditions are milder, and the occurrence of side reactions is reduced to a certain extent, thereby improving the selectivity of fluorination.

[0027] 3. This invention greatly shortens the overall process, completing the synthesis of 2,4,5-trifluorophenylacetic acid in only four steps, including one step of ester hydrolysis. In fact, only three steps need to be studied in detail, which greatly reduces equipment investment.

[0028] 4. This invention uses readily available and inexpensive o-chloronitrobenzene as a raw material, reacting it with sodium nitrate in a sulfuric acid and trifluoroacetic acid system. The resulting 2,4-dinitrochlorobenzene is separated by melt crystallization. This 2,4-dinitrochlorobenzene then undergoes an indirect aromatic nucleophilic substitution reaction under methyl chloroacetate and sodium hydride conditions to generate methyl 5-chloro-2,4-dinitrophenylacetate. After separation, it undergoes a fluorination reaction with potassium fluoride under a phase transfer catalyst. The methyl 2,4,5-trifluorophenylacetate obtained by distillation is then hydrolyzed and acidified in an aqueous sodium hydroxide solution to obtain 2,4,5-trifluorophenylacetic acid. This process is safer, more environmentally friendly, more efficient, and lower in cost. Attached Figure Description

[0029] Figure 1 This is the gas chromatogram of crude 2,4-dinitrochlorobenzene in Example 1 of the present invention;

[0030] Figure 2 This is the gas chromatogram of crude 2,4-dinitrochlorobenzene in Example 2 of the present invention;

[0031] Figure 3 This is the gas chromatogram of crude 2,4-dinitrochlorobenzene in Example 3 of the present invention;

[0032] Figure 4 This is the gas chromatogram of crude 2,4-dinitrochlorobenzene in Example 4 of the present invention;

[0033] Figure 5 This is the gas chromatogram of crude 2,4-dinitrochlorobenzene in Example 5 of the present invention;

[0034] Figure 6 This is the gas chromatogram of crude 2,4-dinitrochlorobenzene in Example 6 of the present invention;

[0035] Figure 7 This is the gas chromatogram of crude 2,4-dinitrochlorobenzene in Example 7 of the present invention;

[0036] Figure 8 This is the gas chromatogram of purified 2,4-dinitrochlorobenzene in Example 8 of the present invention;

[0037] Figure 9 This is the gas chromatogram of crude methyl 5-chloro-2,4-dinitrophenylacetic acid ester in Example 8 of the present invention;

[0038] Figure 10 This is the gas chromatogram of crude methyl 5-chloro-2,4-dinitrophenylacetic acid ester in Example 9 of the present invention;

[0039] Figure 11 This is a gas chromatogram of crude methyl 5-chloro-2,4-dinitrophenylacetic acid ester in Example 10 of the present invention;

[0040] Figure 12 This is the gas chromatogram of methyl 5-chloro-2,4-dinitrophenylacetate obtained in Example 10 of the present invention;

[0041] Figure 13 This is the gas chromatogram of 2,4,5-trifluorophenylacetic acid in Example 11 of the present invention;

[0042] Figure 14 This is the gas chromatogram of 2,4,5-trifluorophenylacetic acid in Example 12 of the present invention;

[0043] Figure 15 This is the gas chromatogram of 2,4,5-trifluorophenylacetic acid in Example 13 of the present invention;

[0044] Figure 16 This is the gas chromatogram of 2,4,5-trifluorophenylacetic acid in Example 14 of the present invention;

[0045] Figure 17 This is the gas chromatogram of 2,4,5-trifluorophenylacetic acid in Example 15 of the present invention;

[0046] Figure 18 This is the gas chromatogram of 2,4,5-trifluorophenylacetic acid in Example 16 of the present invention;

[0047] Figure 19 This is the gas chromatogram of 2,4,5-trifluorophenylacetic acid in Example 17 of the present invention. Detailed Implementation

[0048] The present invention will be further illustrated below with reference to the embodiments.

[0049] Example 1

[0050] 15.76 g of o-chloronitrobenzene and 94.56 g of trifluoroacetic acid were added to a four-necked flask equipped with a thermometer and a mechanical stirrer. After stirring and dissolving, 34.01 g of sodium nitrate was added, followed by 39.24 g of concentrated sulfuric acid. The mixture was stirred and reacted in a water bath at 25 °C for 10 h. The reaction solution was then added dropwise to 200 g of water, and the temperature was raised to 50 °C. The organic phase was separated, washed with alkali and water, and then separated to obtain 18.09 g of crude 2,4-dinitrochlorobenzene with a purity of 89.57% (calculated based on gas chromatographic peak area), with a yield of 79.97%.

[0051] Example 2

[0052] In Example 1, the mass of sodium nitrate was changed to 25.51 g, and the rest of the operation was the same, resulting in 18.56 g of crude 2,4-dinitrochlorobenzene with a purity of 73.92% (calculated by gas chromatographic peak area), with a yield of 67.71%.

[0053] Example 3

[0054] In Example 1, the mass of sodium nitrate was changed to 42.51 g, and the rest of the operation was the same, resulting in 18.33 g of crude 2,4-dinitrochlorobenzene with a purity of 88.34% (calculated by gas chromatographic peak area), with a yield of 79.92%.

[0055] Example 4

[0056] In Example 1, the mass of concentrated sulfuric acid was changed to 29.43 g, and the rest of the operation was the same, yielding 18.23 g of crude 2,4-dinitrochlorobenzene with a purity of 82.68% (calculated by gas chromatographic peak area), with a yield of 74.39%.

[0057] Example 5

[0058] In Example 1, the mass of concentrated sulfuric acid was changed to 49.05 g, and the rest of the operation was the same, resulting in 18.45 g of crude 2,4-dinitrochlorobenzene with a purity of 87.57% (calculated by gas chromatographic peak area), with a yield of 79.74%.

[0059] Example 6

[0060] In Example 1, the reaction time was changed to 8 hours, and the rest of the operation was the same, yielding 16.53 g of crude 2,4-dinitrochlorobenzene with a purity of 91.18% (calculated by gas chromatographic peak area), with a yield of 74.39%.

[0061] Example 7

[0062] In Example 1, the reaction time was changed to 12 hours, and the rest of the operation was the same, yielding 17.96 g of crude 2,4-dinitrochlorobenzene with a purity of 88.65% (calculated by gas chromatographic peak area), with a yield of 78.58%.

[0063] Example 8

[0064] Several batches of the reaction were repeated under the conditions of Example 1. The resulting organic phase was placed in a crystallizer and cooled to 15°C for 3 hours, then heated to 30°C within 3 hours. The resulting crystals were purified 2,4-dinitrochlorobenzene, which was used in the reaction in step S2. The specific purification steps were as follows: the organic phase was placed in the crystallizer, and the material was first heated to 50°C using a high-low temperature integrated machine to completely melt the material. Then, a linear cooling program was set to cool the material to 30°C, with a total cooling of 20°C, taking 120 minutes. Subsequently, a crystal growth process was carried out to obtain crystals in the crystallizer and initiate crystallization. After the crystal growth cooling program was completed, the crystal growth process was carried out. The material was then cooled to 15°C using a linear cooling program, with a total cooling rate of 15°C over 60 minutes. A crystallization process was then performed to purify the material. After the crystallization cooling program, the material was held at this temperature for 30 minutes. After this holding period, residue was discharged from the crystallizer, releasing the low-concentration liquid. The temperature was then increased to 20°C using a linear program over 60 minutes. Finally, a sweating process was performed, with the temperature increased to 30°C using a linear program over 120 minutes, ultimately yielding purified crystals. This method was used to prepare 100g of purified 2,4-dinitrochlorobenzene with a purity of 99.23%.

[0065] Add 20.26 g of the purified 2,4-dinitrochlorobenzene to a four-necked flask equipped with a thermometer and mechanical stirrer after drying. Stir at 300 rpm for 30 min, then add 40.52 g of dimethyl sulfoxide. Slowly add 10.77 g of methyl chloroacetate dropwise while stirring. Replace the air in the flask with nitrogen, and under nitrogen protection, add 5.56 g of 60 wt% sodium hydride (used as a 60% by mass oil dispersion) in 5 portions over 30 min. Sodium hydride (dispersed in mineral oil) was reacted at 25°C for 12 h. The reaction mixture was slowly poured into 100 g of ice water with stirring, extracted with 100 g of ethyl acetate, and washed twice with 50 g of saturated brine. The organic phase was dried with anhydrous sodium sulfate, filtered, and the ethyl acetate was removed by vacuum distillation to obtain 21.23 g of crude methyl 5-chloro-2,4-dinitrophenylacetic acid with a purity of 98.36% (calculated by gas chromatographic peak area), with a yield of 76.61%.

[0066] Example 9

[0067] In Example 8, the mass of methyl chloroacetate was changed to 11.85 g, and the rest of the operation was the same, to obtain 23.64 g of crude methyl 5-chloro-2,4-dinitrophenylacetate with a purity of 98.07% (calculated by gas chromatography peak area), with a yield of 85.06%.

[0068] Example 10

[0069] In Example 8, the mass of methyl chloroacetate was changed to 12.93 g, and the rest of the operation was the same, yielding 23.58 g of crude methyl 5-chloro-2,4-dinitrophenylacetate with a purity of 97.31% (calculated by gas chromatography peak area), with a yield of 84.18%.

[0070] Several batches of the reaction were repeated under the conditions of Example 10, and a total of about 500g of methyl 5-chloro-2,4-dinitrophenylacetate with a purity of 97.96% was collected and used as the raw material for the following examples.

[0071] Example 11

[0072] Add 27.80 g of the above-mentioned methyl 5-chloro-2,4-dinitrophenylacetate to a four-necked flask, then add 55.60 g of sulfolane, and add 18.99 g of spray-dried potassium fluoride at 150 rpm. Adjust the stirring speed to 200 rpm, then add 40.23 g of phthaloyl chloride, followed by 0.83 g of tetramethylammonium chloride. Raise the temperature to 160 °C, adjust the stirring speed to 300 rpm, and react for 3 h. Then adjust the stirring speed to 500 rpm and continue reacting for 5 h. After the reaction is complete, cool to room temperature. The sample was washed with 140g of water to separate the aqueous phase. The oil phase was then separated by distillation to obtain methyl 2,4,5-trifluorophenylacetate. The obtained methyl 2,4,5-trifluorophenylacetate was then added to 47.55g of 10wt% sodium hydroxide aqueous solution and hydrolyzed by stirring in a water bath at 60℃ for 4h. After cooling to room temperature, the solution was acidified with sulfuric acid to pH=2. After filtration, washing with water, and drying, 10.59g of 2,4,5-trifluorophenylacetic acid with a purity of 99.42% (calculated based on gas chromatographic peak area) was obtained, with a yield of 55.84%.

[0073] Example 12

[0074] In Example 11, the amount of potassium fluoride was changed to 20.14 g, and the rest of the operation was the same, resulting in 11.67 g of 2,4,5-trifluorophenylacetic acid with a purity of 99.06% (calculated by gas chromatographic peak area), with a yield of 61.31%.

[0075] Example 13

[0076] In Example 11, the amount of potassium fluoride was changed to 21.30 g, and the rest of the operation was the same, resulting in 11.83 g of 2,4,5-trifluorophenylacetic acid with a purity of 98.27% (calculated by gas chromatographic peak area), with a yield of 61.66%.

[0077] Example 14

[0078] In Example 12, the reaction temperature was changed to 140°C, and the rest of the operation was the same, yielding 10.94 g of 2,4,5-trifluorophenylacetic acid with a purity of 98.93% (calculated by gas chromatographic peak area), with a yield of 57.40%.

[0079] Example 15

[0080] In Example 11, the reaction temperature was changed to 150°C, and the rest of the operation was the same, yielding 12.06 g of 2,4,5-trifluorophenylacetic acid with a purity of 99.44% (calculated by gas chromatographic peak area), with a yield of 63.61%.

[0081] Example 16

[0082] In Example 15, the reaction time was changed to 9 hours, and the rest of the operation was the same, yielding 12.46 g of 2,4,5-trifluorophenylacetic acid with a purity of 99.81% (calculated by gas chromatographic peak area), with a yield of 65.96%.

[0083] Example 17

[0084] In Example 15, the reaction time was changed to 10 h, and the rest of the operation was the same, yielding 12.61 g of 2,4,5-trifluorophenylacetic acid with a purity of 98.68% (calculated by gas chromatographic peak area), with a yield of 66.00%.

[0085] It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the teachings of this invention, those skilled in the art can make various alterations or modifications to the invention, and these equivalent forms also fall within the scope defined by the appended claims.

Claims

1. A method for synthesizing 2,4,5-trifluorophenylacetic acid, characterized in that... Includes the following steps: S1: Add o-chloronitrobenzene and trifluoroacetic acid to the reactor, stir to dissolve, and then add sodium nitrate and concentrated sulfuric acid. React at 25°C for 8-12 hours. Add the reaction liquid dropwise to water, heat to 50°C, separate the organic phase, and obtain 2,4-dinitrochlorobenzene. S2: 2,4-Dinitrochlorobenzene was added to the reaction vessel, followed by dimethyl sulfoxide. Methyl chloroacetate was added dropwise with stirring. Sodium hydride was added in portions (5 portions over 30 min) under nitrogen protection. The reaction was carried out at 25°C for 12 h. The reaction mixture was poured into ice water with stirring and extracted with ethyl acetate to obtain methyl 5-chloro-2,4-dinitrophenylacetate. S3: 5-chloro-2,4-dinitrophenylacetic acid methyl ester was added to the reactor, followed by sulfolane. While stirring, potassium fluoride, phthaloyl chloride and tetramethylammonium chloride were added. The temperature was raised to 140-160℃ and reacted for 8-10 hours. After the reaction was completed, the temperature was lowered to room temperature. The aqueous phase was separated by washing with water, and the oil phase was separated by distillation to obtain 2,4,5-trifluorophenylacetic acid methyl ester. S4: Methyl 2,4,5-trifluorophenylacetic acid was added to an aqueous sodium hydroxide solution and hydrolyzed at 60°C for 4 hours. After cooling to room temperature, the pH was adjusted to 2, and the mixture was filtered, washed with water, and dried to obtain 2,4,5-trifluorophenylacetic acid.

2. The method for synthesizing 2,4,5-trifluorophenylacetic acid as described in claim 1, characterized in that: In step S1, the mass ratio of o-chloronitrobenzene to trifluoroacetic acid is 1:6, and the molar ratio of o-chloronitrobenzene, sodium nitrate, and concentrated sulfuric acid is 1:3 to 5:3 to 5.

3. The method for synthesizing 2,4,5-trifluorophenylacetic acid as described in claim 1, characterized in that: The organic phase obtained in step S1 is placed in a crystallizer and cooled to 15°C for 3 hours. Then, the temperature is raised to 30°C within 3 hours. The resulting crystal is purified 2,4-dinitrochlorobenzene, which is used in the reaction in step S2.

4. The method for synthesizing 2,4,5-trifluorophenylacetic acid as described in claim 3, characterized in that: The residual liquid and sweat discharged from the bottom of the crystallizer during the crystallization process are collected, and 2,4-dinitrochlorobenzene is recovered after crystallization and separation.

5. The method for synthesizing 2,4,5-trifluorophenylacetic acid as described in claim 1, characterized in that: In step S2, the mass ratio of 2,4-dinitrochlorobenzene to dimethyl sulfoxide is 1:

2.

6. The method for synthesizing 2,4,5-trifluorophenylacetic acid as described in claim 1, characterized in that: In step S2, the molar ratio of 2,4-dinitrochlorobenzene, methyl chloroacetate, and sodium hydride is 1:1.0 to 1.2:1.4, wherein sodium hydride is used in the form of 60 wt% oil dispersion.

7. The method for synthesizing 2,4,5-trifluorophenylacetic acid as described in claim 1, characterized in that: In step S2, the reaction solution is extracted with ethyl acetate, washed with saturated brine 1-3 times, dried with anhydrous sodium sulfate, filtered, and the ethyl acetate is removed by vacuum distillation to obtain methyl 5-chloro-2,4-dinitrophenylacetate.

8. The method for synthesizing 2,4,5-trifluorophenylacetic acid as described in claim 1, characterized in that: In step S3, the mass ratio of methyl 5-chloro-2,4-dinitrophenylacetate, sulfolane, and tetramethylammonium chloride is 1:2:0.

03.

9. The method for synthesizing 2,4,5-trifluorophenylacetic acid as described in claim 1, characterized in that: In step S3, the molar ratio of methyl 5-chloro-2,4-dinitrophenylacetate, potassium fluoride, and phthaloyl chloride is 1:3.3-3.7:

2.

10. The method for synthesizing 2,4,5-trifluorophenylacetic acid as described in claim 1, characterized in that: In step S4, the molar ratio of methyl 2,4,5-trifluorophenylacetate to sodium hydroxide is 1:1.2, and the concentration of the sodium hydroxide aqueous solution is 10-15 wt%.

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