A method for synthesizing 2,4,5-trifluorophenylacetic acid

Abstract

The application discloses a synthesis method of 2,4,5-trifluorophenylacetic acid, and relates to the technical field of organic chemical industry. The method comprises the following steps: starting from 2,4-dichloro-5-fluorobenzoyl chloride, first performing cyanoization to generate 2,4-dichloro-5-fluorobenzoyl cyanide, then performing halogen exchange reaction with potassium fluoride under the condition of a phase transfer catalyst to generate 2,4,5-trifluorobenzoyl cyanide, then reducing under p-toluenesulfonyl hydrazide and sodium borohydride, and finally hydrolyzing under an acidic condition to generate 2,4,5-trifluorophenylacetic acid. The method has high selectivity and purity, and is lower in cost.

Description

Technical Field

[0001] This invention relates to the field of organic chemical technology, 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-IV inhibitor developed by Merck & Co., Inc. It was approved by the U.S. Food and Drug Administration (FDA) in October 2006 and is highly selective with moderate hypoglycemic effects, making it one of the best-selling diabetes medications on the market. In addition, 2,4,5-trifluorophenylacetic acid is also an important intermediate in the synthesis of novel fluorinated herbicides.

[0003] Currently, there are numerous routes for synthesizing trifluorophenylacetic acid in China, mainly using 1,2,4-trifluorobenzene as the starting material. There are also a few reports of synthesizing trifluorophenylacetic acid using 2,4,5-trifluoroaniline, 2,4,5-trifluorobromobenzene, tetrachlorophthalic anhydride, and tetrafluoroterephthalic acid as starting materials.

[0004] Chinese patent CN101659611B discloses a method for preparing 2,4,5-trifluorophenylacetic acid, which uses 1,2,4-trifluorobenzene as the starting material, and then performs chloromethylation, cyanation, and hydrolysis under acidic conditions to produce trifluorophenylacetic acid (as shown in the figure below). In this method, the chloromethylation step uses a strong acid, which is highly corrosive and causes serious pollution. In addition, chloromethylation produces isomers that are difficult to separate. Similar literature reports include: Chinese patent CN100516014C discloses a method for preparing 2,4,5-trifluorophenylacetic acid, in which benzyl chloride reacts with carbon monoxide under the action of a cobalt tetracarbonyl salt catalyst, and finally hydrolyzes to produce 2,4,5-trifluorophenylacetic acid. However, this method involves high-pressure reaction, and the cobalt tetracarbonyl salt catalyst used is expensive. Chinese patent CN102584565B discloses a method for preparing 2,4,5-trifluorophenylacetic acid, in which chloroacetonitrile is used instead of paraformaldehyde and sodium chloride to prepare 2,4,5-trifluorophenylacetonitrile via Friedel-Crafts alkylation reaction, followed by hydrolysis to produce 2,4,5-trifluorophenylacetic acid. This method uses Lewis acid, which causes serious pollution, and the Friedel-Crafts alkylation yield is low, making it difficult to stop at the monosubstituted product.

[0005] Chinese patent CN106928044B discloses a method for preparing fluorophenylacetic acid. Starting from 2,4,5-trifluoroaniline, the method involves diazotization and addition denitrification of vinylidene chloride to generate a fluorobenzene-substituted trichloroethane intermediate, which is then hydrolyzed to 2,4,5-trifluorophenylacetic acid (as shown in the figure below). Although this method avoids the use of toxic sodium cyanide, the first step involves a significant amount of diazonium salt and chloride ions undergoing a Sandmeier reaction to generate 2,4,5-trifluorochlorobenzene impurities, increasing separation costs. Furthermore, the price of 1,1-dichloroethylene and the copper salt catalyst is not competitive.

[0006] The literature “A new economical and efficient method for preparing 2,4,5-trifluorophenylacetic acid [J]. Zhejiang Chemical Industry, 2022, 52, 9-11” reports a method for obtaining high-purity 2,4,5-trifluorophenylacetic acid by using diethyl 2,3,5,6-tetrafluoroterephthalate and diethyl malonate or ethyl cyanoacetate as starting materials through a three-step reaction of nucleophilic substitution, hydrolysis, and decarboxylation (as shown in the figure below). However, it has poor atom economy and high cost. Other methods for preparing 2,4,5-trifluorophenylacetic acid that have low feasibility or are currently obsolete will not be detailed here.

[0007] Overall, the mainstream process currently uses 1,2,4-trifluorobenzene or 2,4,5-trifluoroaniline prepared from 2,4-dichlorofluorobenzene as the starting point. The preparation route is as follows: 2,4-dichlorofluorobenzene is nitrated, fluorinated, and reduced to prepare 2,4,5-trifluoroaniline, and then 1,2,4-trifluorobenzene is prepared by a diazotization deammoniation step. However, this route has many problems. First, nitration carries a significant safety risk. Second, the fluorination of 2,4-dichloro-5-fluoronitrobenzene is prone to fluorination of nitro groups and a series of other side reactions caused by the removed nitro group attacking the benzene ring. As a result, this step can only obtain the target product 2,4,5-trifluoronitrobenzene in a low to medium yield (around 60%), and there are many byproducts that are difficult to separate. The prices of 1,2,4-trifluorobenzene and 2,4,5-trifluoroaniline prepared from 2,4-dichlorofluorobenzene remain high, which in turn makes the price of 2,4,5-trifluorophenylacetic acid too high. Summary of the Invention

[0008] The technical problem to be solved by the present invention is to provide a method for synthesizing 2,4,5-trifluorophenylacetic acid with high selectivity and purity and lower cost, in order to address the shortcomings of the existing technology.

[0009] To solve the above-mentioned technical problems, the technical solution of the present invention is as follows:

[0010] A method for synthesizing 2,4,5-trifluorophenylacetic acid includes the following steps:

[0011] A: Add solid sodium cyanide, toluene, catalyst and reaction aid to the reactor and stir until homogeneous. Then add 2,4-dichloro-5-fluorobenzoyl chloride dropwise. After the addition is complete, heat and reflux for 4 hours. Add ice water to quench the solution, stir and separate the liquids. Distill the organic phase to obtain 2,4-dichloro-5-fluorobenzoyl nitrile.

[0012] B: 2,4-Dichloro-5-fluorobenzonitrile, solvent and phase transfer catalyst were added to the reactor and stirred evenly. Potassium fluoride was added and the reaction was kept at the temperature for 5 hours. After the reaction was completed, the temperature was lowered and the mixture was washed with deionized water. The liquid was separated and the organic phase was distilled to obtain 2,4,5-trifluorobenzonitrile.

[0013] C: Add 2,4,5-trifluorobenzoyl nitrile, p-toluenesulfonyl hydrazine and methanol to the reactor, reflux for 6-8 hours, stop the reaction, distill the crude product in the bottom liquid and dissolve it in toluene, add sodium borohydride, reflux for 6-8 hours and stop the reaction, quench with ice water, separate the liquid and distill the organic phase to obtain 2,4,5-trifluorophenylacetonitrile;

[0014] D: Add 2,4,5-trifluorophenylacetonitrile and acidic water to the reactor, heat to 90-110℃, and after complete hydrolysis, cool to 50℃, add deionized water, continue to cool to 10℃, filter, wash with water, recrystallize and dry to obtain 2,4,5-trifluorophenylacetic acid.

[0015] The reaction route is as follows:

[0016] Preferably, in step A, the molar ratio of 2,4-dichloro-5-fluorobenzoyl chloride to solid sodium cyanide is 1:1.0-1.2, and the mass ratio of 2,4-dichloro-5-fluorobenzoyl chloride to toluene, catalyst and auxiliaries is 1:2:1-5:0.5.

[0017] Preferably, during the addition of 2,4-dichloro-5-fluorobenzoyl chloride in step A, the temperature inside the reactor is controlled at 25-30°C, and after the addition is completed, the reflux temperature is raised to 100-110°C.

[0018] Preferably, the catalyst in step A is polyethylene glycol-400, and the reaction aid is glycerol.

[0019] Preferably, the solvent in step B is sulfolane and the phase transfer catalyst is tetramethylammonium chloride.

[0020] Preferably, in step B, the mass ratio of 2,4-dichloro-5-fluorobenzonitrile to solvent and phase transfer catalyst is 1:1.5:0.5-5.0, and the molar ratio of 2,4-dichloro-5-fluorobenzonitrile to potassium fluoride is 1:2.0-2.5.

[0021] Preferably, in step B, after stirring evenly and heating to 80°C, potassium fluoride is added, and the reaction temperature is maintained at 160-200°C after adding potassium fluoride.

[0022] Preferably, in step C, the molar ratio of 2,4,5-trifluorobenzoyl nitrile to p-toluenesulfonyl hydrazine and sodium borohydride is 1:1.1-1.5:2-3, and the mass ratio of 2,4,5-trifluorobenzoyl nitrile to methanol is 1:2.

[0023] Preferably, in step C, the reflux temperature after adding 2,4,5-trifluorobenzoyl nitrile, p-toluenesulfonyl hydrazine and methanol is 60-70°C, and the reflux temperature after adding sodium borohydride is 100-110°C.

[0024] Preferably, the acidic water in step D is a hydrochloric acid solution or a sulfuric acid solution, wherein the mass ratio of 2,4,5-trifluorophenylacetonitrile to the solute in the acidic water and deionized water is 1:3.4-3.5:5.

[0025] Due to the adoption of the above technical solution, the beneficial effects of the present invention are:

[0026] This invention starts with readily available and inexpensive 2,4-dichloro-5-fluorobenzoyl chloride (2,4-dichloro-5-fluorobenzoyl chloride is the main raw material for preparing the antipsychotic drugs trifluoroguanidine alcohol, trifluoroguanidine, and pentaflulide, as well as for synthesizing broad-spectrum antibiotics such as ciprofloxacin and other third-generation quinolone drugs). First, cyano-coating is used to synthesize 2,4-dichloro-5-fluorobenzoyl nitrile. Then, fluorination is performed under phase-transfer catalyst conditions to prepare 2,4,5-trifluorobenzoyl nitrile. This is then reduced to 2,4,5-trifluorophenylacetonitrile using p-toluenesulfonyl hydrazine and sodium borohydride, and finally hydrolyzed under acidic conditions to 2,4,5-trifluorophenylacetic acid. Compared to other processes for synthesizing trifluorophenylacetic acid from 1,2,4-trifluorobenzene and 2,4,5-trifluoroaniline obtained from 2,4-dichlorofluorobenzene, this route avoids the nitration of fluorochlorobenzene, greatly reducing the safety risks of the reaction. At the same time, compared with the fluorination of 2,4-dichloro-5-fluoronitrobenzene, 2,4-dichloro-5-fluorobenzoyl nitrile has a higher degree of activation of the chlorine atom on the aromatic ring due to the superposition of the strong electron-withdrawing carbonyl and cyano groups, making it more prone to halogen exchange fluorination reaction. It does not have the side reaction of fluorine substitution of carbonyl group (the fluorination of chloronitrobenzene will have the side reaction of fluorinated nitro group, and the nitro group that falls off will continue to attack the benzene ring, producing more impurities). It also avoids the problem of isomer separation of chloromethylation, resulting in higher selectivity and yield, better product quality, and lower cost. Attached Figure Description

[0027] Figure 1 This is the gas chromatogram of 2,4-dichloro-5-fluorobenzonitrile in Example 1 of the present invention;

[0028] Figure 2 This is the gas chromatogram of 2,4-dichloro-5-fluorobenzonitrile in Example 2 of the present invention;

[0029] Figure 3 This is the gas chromatogram of 2,4-dichloro-5-fluorobenzonitrile in Example 3 of the present invention;

[0030] Figure 4 This is the gas chromatogram of 2,4,5-trifluorobenzoyl nitrile in Example 4 of the present invention;

[0031] Figure 5 This is the gas chromatogram of 2,4,5-trifluorobenzoyl nitrile in Example 5 of the present invention;

[0032] Figure 6 This is the gas chromatogram of 2,4,5-trifluorobenzoyl nitrile in Example 6 of the present invention;

[0033] Figure 7 This is the gas chromatogram of 2,4,5-trifluorobenzoyl nitrile in Example 7 of the present invention;

[0034] Figure 8 This is the gas chromatogram of 2,4,5-trifluorobenzoyl nitrile in Example 8 of the present invention;

[0035] Figure 9 This is the gas chromatogram of 2,4,5-trifluorobenzonitrile in Example 9 of the present invention;

[0036] Figure 10 This is the gas chromatogram of 2,4,5-trifluorophenylacetonitrile in Example 10 of the present invention;

[0037] Figure 11 This is the gas chromatogram of 2,4,5-trifluorophenylacetonitrile in Example 12 of the present invention;

[0038] Figure 12 This is the gas chromatogram of 2,4,5-trifluorophenylacetonitrile in Example 12 of the present invention;

[0039] Figure 13 This is the gas chromatogram of 2,4,5-trifluorophenylacetonitrile in Example 13 of the present invention;

[0040] Figure 14 This is the gas chromatogram of 2,4,5-trifluorophenylacetonitrile in Example 14 of the present invention;

[0041] Figure 15 This is the gas chromatogram of 2,4,5-trifluorophenylacetic acid in Example 15 of the present invention;

[0042] Figure 16 This is the gas chromatogram of 2,4,5-trifluorophenylacetic acid in Example 16 of the present invention;

[0043] Figure 17 This is the gas chromatogram of 2,4,5-trifluorophenylacetic acid in Example 17 of the present invention;

[0044] Figure 18 This is the NMR spectrum of 2,4,5-trifluorophenylacetonitrile in Example 10 of the present invention;

[0045] Figure 19 This is the NMR spectrum of 2,4,5-trifluorophenylacetic acid in Example 15 of the present invention;

[0046] Figure 20 This is a liquid chromatography-mass spectrometry (LC-MS) diagram of 2,4,5-trifluorophenylacetonitrile in Example 10 of the present invention;

[0047] Figure 21 This is a liquid chromatography-mass spectrometry (LC-MS) diagram of 2,4,5-trifluorophenylacetic acid in Example 15 of this invention;

[0048] Figure 22 This is the gas chromatography-mass spectrometry (GC) chromatogram of 2,4,5-trifluorobenzoyl nitrile in Example 9 of this invention. Detailed Implementation

[0049] The present invention will be further illustrated below with reference to the embodiments. Example 1

[0050] Preparation of 2,4-dichloro-5-fluorobenzonitrile

[0051] 14.17 g of solid sodium cyanide, 140 g of toluene, 0.68 g of polyethylene glycol-400, and 0.34 g of glycerol were added to a four-necked flask equipped with a thermometer and a mechanical stirrer. 68.24 g of 2,4-dichloro-5-fluorobenzoyl chloride was added dropwise while maintaining the temperature at 25-30 °C. After the addition was complete, the temperature was slowly raised to 100-110 °C for reflux reaction with toluene for 4 hours. After the reaction was complete, 140 g of ice water was added to quench the reaction. The mixture was stirred and separated. The organic phase was distilled to obtain 58.8 g of 2,4-dichloro-5-fluorobenzoyl nitrile, with a yield of 89.9% and a purity of 96.48%. Toluene was recovered simultaneously. The aqueous phase was reacted with 25% hydrogen peroxide to remove residual sodium cyanide. Example 2

[0052] The amount of solid sodium cyanide added in Example 1 was changed to 16.2g and the amount of polyethylene glycol-400 added was changed to 1.7g. The rest of the operation was the same. Organic phase distillation yielded 63.5g of 2,4-dichloro-5-fluorobenzonitrile, with a yield of 97.1% and a purity of 99.24%. Example 3

[0053] The dosage of polyethylene glycol-400 in Example 2 was changed to 3.4g, and the rest of the operation was the same. Organic phase distillation yielded 63.4g of 2,4-dichloro-5-fluorobenzoyl nitrile, with a yield of 97.0% and a purity of 99.15%. Example 4

[0054] Preparation of 2,4,5-trifluorobenzoyl nitrile

[0055] 2,4-Dichloro-5-fluorobenzonitrile was accumulated according to the method in Example 2.

[0056] 65.4 g of 2,4-dichloro-5-fluorobenzoyl nitrile, 98.1 g of sulfolane, and 0.3270 g of tetramethylammonium chloride were added to a four-necked flask equipped with a thermometer and a mechanical stirrer. The mixture was stirred until homogeneous and heated to 80°C. Then, 34.86 g of potassium fluoride was added, and the temperature was further increased to 200°C. The reaction was maintained at this temperature for 5 hours. After the reaction was completed, the material was allowed to cool slightly and then washed once with water at twice the mass equivalent of the liquid. The salt, phase transfer catalyst, and solvent in the system were removed by separation. The organic phase was collected and distilled to obtain 36.2 g of 2,4,5-trifluorobenzoyl nitrile, with a yield of 65.1% and a purity of 97.63%. Example 5

[0057] The amount of tetramethylammonium chloride added in Example 4 was changed to 1.635g, and the rest of the operation was the same. After the reaction was completed, the material was washed once with water with twice the mass equivalent of the liquid after the material cooled down slightly. The salt, phase transfer catalyst and solvent in the system were removed by separation. The organic phase was collected and distilled to obtain 40.9g of 2,4,5-trifluorobenzonitrile, with a yield of 73.6% and a purity of 98.93%. Example 6

[0058] The amount of tetramethylammonium chloride added in Example 4 was changed to 3.27g, and the rest of the operation was the same. After the reaction was completed, the material was washed once with water with twice the mass equivalent of the liquid after the material cooled down slightly. The salt, phase transfer catalyst and solvent in the system were removed by separation. The organic phase was collected and distilled to obtain 41.2g of 2,4,5-trifluorobenzoyl nitrile, with a yield of 74.2% and a purity of 98.68%. Example 7

[0059] In Example 5, the amount of potassium fluoride added was changed to 38.3g, and the rest of the operation was the same. After the material cooled down slightly, it was washed once with water with twice the mass equivalent of the material liquid. The salt, phase transfer catalyst and solvent in the system were removed by separation. The organic phase was collected and distilled to obtain 44.1g of 2,4,5-trifluorobenzonitrile, with a yield of 79.5% and a purity of 99.06%. Example 8

[0060] The fluorination reaction temperature in Example 7 was changed to 160°C, and the rest of the operation was the same. After the material cooled down slightly, it was washed once with water with two times the mass equivalent of the liquid. The salt, phase transfer catalyst and solvent in the system were removed by separation. The organic phase was collected and distilled to obtain 43.8g of 2,4,5-trifluorobenzonitrile, with a yield of 78.9% and a purity of 99.44%. Example 9

[0061] The fluorination reaction temperature in Example 7 was changed to 170°C, and the rest of the operation was the same. After the material cooled down slightly, it was washed once with water with two times the mass equivalent of the liquid. The salt, phase transfer catalyst and solvent in the system were removed by separation. The organic phase was collected and distilled to obtain 47.0 g of 2,4,5-trifluorobenzonitrile, with a yield of 84.7% and a purity of 99.81%. Example 10

[0062] Preparation of 2,4,5-trifluorophenylacetonitrile

[0063] 2,4,5-trifluorobenzoyl nitrile was accumulated according to the method in Example 9.

[0064] 55.5 g of 2,4,5-trifluorobenzoyl nitrile and 61.5 g of p-toluenesulfonyl hydrazine were added to a four-necked flask equipped with a thermometer and a mechanical stirrer. 110 g of methanol was added to dissolve them. The mixture was refluxed at 60-70 °C for 6-8 h and then the reaction was stopped. Methanol and other low-boiling impurities were removed by distillation. The crude product in the distillate was dissolved in 100 g of toluene. 22.7 g of sodium borohydride was added in 3-5 portions. The temperature was slowly raised to 100-110 °C and refluxed for 6-8 h. The reaction was stopped by adding small amounts of ice water in multiple batches to quench the reaction. The mixture was separated, extracted with toluene, and the combined organic phases were distilled to recover toluene. 36.0 g of 2,4,5-trifluorophenylacetonitrile was obtained with a purity of 98.81% and a yield of 70.1%. Example 11

[0065] The amount of p-toluenesulfonyl hydrazine added in Example 10 was changed to 72.6 g, and the rest of the operation was the same. After the reaction was completed, 38.7 g of 2,4,5-trifluorophenylacetonitrile was obtained with a purity of 98.67% and a yield of 75.3%. Example 12

[0066] The amount of p-toluenesulfonyl hydrazine added in Example 10 was changed to 83.8g, and the rest of the operation was the same. After the treatment was completed, 38.6g of 2,4,5-trifluorophenylacetonitrile was obtained with a purity of 98.69% and a yield of 75.2%. Example 13

[0067] In Implementation Case 11, the amount of sodium borohydride added was changed to 28.4g, and the rest of the operation was the same. After the procedure was completed, 42.7g of 2,4,5-trifluorophenylacetonitrile was obtained with a purity of 99.56% and a yield of 83.1%. Example 14

[0068] In Example 11, the amount of sodium borohydride added was changed to 34.0 g, and the rest of the operation was the same. After the reaction was completed, 42.8 g of 2,4,5-trifluorophenylacetonitrile was obtained with a purity of 98.85% and a yield of 83.3%. Example 15

[0069] Preparation of 2,4,5-trifluorophenylacetic acid

[0070] 2,4,5-trifluorophenylacetonitrile was prepared according to the procedure in Example 13.

[0071] 51.3 g of 2,4,5-trifluorophenylacetonitrile and 500 g of 35% wt hydrochloric acid aqueous solution were added to a four-necked flask equipped with a thermometer and a mechanical stirrer. The temperature was raised to 90 °C. During the reaction, samples of the liquid phase were taken every 2 hours to qualitatively monitor whether the hydrolysis was complete until the hydrolysis was complete. The reaction was stopped after 6 hours of incubation. The temperature was lowered to 50 °C, and 5 times the mass equivalent of water was added. The temperature was further lowered to 10 °C, filtered, washed with water, recrystallized, and dried to obtain 45.8 g of 2,4,5-trifluorophenylacetic acid with a purity of 99.13% and a yield of 80.22%. Example 16

[0072] In Example 15, the acid water was replaced with 250g of 72%wt sulfuric acid aqueous solution, and other operations were the same. After the reaction was completed, the post-treatment yielded 54.5g of 2,4,5-trifluorophenylacetic acid with a purity of 99.36% and a yield of 95.5%. Example 17

[0073] Preparation of 2,4,5-trifluorophenylacetic acid

[0074] In Example 16, the reaction temperature was changed to 110°C, and other operations were the same. After the reaction was completed, the post-treatment yielded 55.7 g of 2,4,5-trifluorophenylacetic acid with a purity of 99.57% and a yield of 97.7%.

[0075] 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: A: Add solid sodium cyanide, toluene, catalyst and reaction aid to the reactor and stir until homogeneous. Then add 2,4-dichloro-5-fluorobenzoyl chloride dropwise. After the addition is complete, heat and reflux for 4 hours. Add ice water to quench the solution, stir and separate the liquids. Distill the organic phase to obtain 2,4-dichloro-5-fluorobenzoyl nitrile. B: 2,4-Dichloro-5-fluorobenzonitrile, solvent and phase transfer catalyst were added to the reactor and stirred evenly. Potassium fluoride was added and the reaction was kept at the temperature for 5 hours. After the reaction was completed, the temperature was lowered and the mixture was washed with deionized water. The liquid was separated and the organic phase was distilled to obtain 2,4,5-trifluorobenzonitrile. C: Add 2,4,5-trifluorobenzoyl nitrile, p-toluenesulfonyl hydrazine, and methanol to the reactor. After refluxing for 6-8 hours, stop the reaction. After distillation, dissolve the crude product in toluene in the bottom liquid. Continue to add sodium borohydride, reflux for 6-8 hours, and then stop the reaction. Quench with ice water, separate the liquids, and distill the organic phase to obtain 2,4,5-trifluorophenylacetonitrile. The molar ratio of 2,4,5-trifluorobenzoyl nitrile to p-toluenesulfonyl hydrazine and sodium borohydride is 1:1.1-1.5:2-3, and the mass ratio of 2,4,5-trifluorobenzoyl nitrile to methanol is 1:

2. D: Add 2,4,5-trifluorophenylacetonitrile and acidic water to the reactor, heat to 90-110℃, and after complete hydrolysis, cool to 50℃, add deionized water, continue to cool to 10℃, filter, wash with water, recrystallize and dry 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 A, the molar ratio of 2,4-dichloro-5-fluorobenzoyl chloride to solid sodium cyanide is 1:1.0-1.2, and the mass ratio of 2,4-dichloro-5-fluorobenzoyl chloride to toluene, catalyst and auxiliaries is 1:2:1-5:0.

5.

3. The method for synthesizing 2,4,5-trifluorophenylacetic acid as described in claim 1, characterized in that: In step A, the temperature inside the reactor is controlled at 25-30℃ during the dropwise addition of 2,4-dichloro-5-fluorobenzoyl chloride, and the reflux temperature is raised to 100-110℃ after the dropwise addition is completed.

4. The method for synthesizing 2,4,5-trifluorophenylacetic acid as described in claim 1, characterized in that: The catalyst mentioned in step A is polyethylene glycol-400, and the reaction aid is glycerol.

5. The method for synthesizing 2,4,5-trifluorophenylacetic acid as described in claim 1, characterized in that: The solvent in step B is sulfolane, and the phase transfer catalyst is tetramethylammonium chloride.

6. The method for synthesizing 2,4,5-trifluorophenylacetic acid as described in claim 1, characterized in that: In step B, the mass ratio of 2,4-dichloro-5-fluorobenzonitrile to solvent and phase transfer catalyst is 1:1.5:0.5-5.0, and the molar ratio of 2,4-dichloro-5-fluorobenzonitrile to potassium fluoride is 1:2.0-2.

5.

7. The method for synthesizing 2,4,5-trifluorophenylacetic acid as described in claim 1, characterized in that: After stirring evenly and heating to 80°C in step B, potassium fluoride is added. After adding potassium fluoride, the reaction temperature is maintained at 160-200°C.

8. The method for synthesizing 2,4,5-trifluorophenylacetic acid as described in claim 1, characterized in that: In step C, the reaction reflux temperature after adding 2,4,5-trifluorobenzoyl nitrile, p-toluenesulfonyl hydrazine and methanol is 60-70℃, and the reaction reflux temperature after adding sodium borohydride is 100-110℃.

9. The method for synthesizing 2,4,5-trifluorophenylacetic acid as described in claim 1, characterized in that: In step D, the acid solution is either hydrochloric acid or sulfuric acid, wherein the mass ratio of 2,4,5-trifluorophenylacetonitrile to the solute in the acid solution and deionized water is 1:3.4-3.5:5.

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