Preparation method of Flupyroxystrobin

Abstract

The invention belongs to the technical field of pesticide synthesis, and particularly relates to a preparation method of Flupyroxystrobin. According to the method, 2-chloro-4-trifluoromethylpyridine and phenol are taken as initial raw materials, etherification reaction, condensation reduction reaction, formylation reaction and one-step alkylation are performed to prepare the Flupyroxystrobin, and the method is simple in synthesis, easy to operate, high in safety coefficient, low in cost and suitable for industrial production.

Description

Technical Field

[0001] The invention belongs to the technical field of pesticide synthesis, and particularly relates to a method for preparing Flupyroxystrobin. Background Art

[0002] Strobilurin pesticides refer to insecticides and fungicides with methoxyacrylate as the main active ingredient. In particular, as fungicide pesticides, they have the characteristics of broad spectrum, high efficiency and low toxicity. For example, azoxystrobin, picoxystrobin, kresoxim-methyl, trifloxystrobin, etc. are increasingly widely used in agricultural production. As an insecticide, Flupyroxystrobin is the first methoxyacrylate insecticide (non-acaricide), which was discovered by the British Imperial Chemical Industries and developed by its successor company Syngenta. Its future market is promising. Strobilurin pesticides often need to be used interchangeably with other agents to avoid the development of drug resistance. As an insecticide, Flupyroxystrobin has no cross-resistance with pyrethroid insecticides, and has a synergistic effect with the metabolites of flonicamid on knocking down and killing Anopheles stephensi. Its IUPAC name: (2E)-3-methoxy-2-(2-{[4-(trifluoromethyl)-2-pyridyl]oxy}phenyl) methyl acrylate, the structure is as follows:

[0003]

[0004] In the prior art, the synthesis of Flupyroxystrobin mainly includes:

[0005] Method 1: WO2016193267 uses 2-chloro-6-fluoro-4-(trifluoromethyl)pyridine and E-2-(2-hydroxyphenyl)-3-methoxy-2-propenoic acid methyl ester in DMF solution, and potassium carbonate is used to obtain E-2-[2-[[6-chloro-4-(trifluoroethyl)-2-pyridyl]oxy]phenyl]-3-methoxy-2-propionate with a yield of 52%, and then in methanol solution, 10% palladium carbon and ammonium formate are reduced at 60 degrees Celsius to obtain Flupyroxystrobin with a yield of 66%. In this process route, 2-chloro-6-fluoro-4-(trifluoromethyl)pyridine and E-2-(2-hydroxyphenyl)-3-methoxy-2-enoic acid methyl ester are expensive and difficult to obtain, and the comprehensive yield of the two steps is only 34%. The synthetic route is as follows:

[0006]

[0007] Method 2: CN111278812 reported that 2-chloro-6-chloro-4-(trifluoromethyl)pyridine and 2-(2-hydroxyphenyl)-3,3-dimethoxy-propionic acid methyl ester were synthesized in DMF solution at room temperature under the action of potassium carbonate and DABCO with a yield of 40%. Subsequently, methyloxy was eliminated in acetic anhydride solvent under the catalysis of methanesulfonic acid. The final product Flupyroxystrobin is obtained with a yield of 79%. In this process route, although 2-chloro-6-chloro-4-(trifluoromethyl)pyridine is cheaper than 2-chloro-6-fluoro-4-(trifluoromethyl)pyridine, it is still expensive. Similarly, the raw material of 2-(2-hydroxyphenyl)-3,3-dimethoxy-propionic acid methyl ester is difficult to synthesize, it is a non-industrial chemical raw material, and the price is high. Acetic anhydride is an easy-to-make drug raw material, and the comprehensive yield of the two steps is only about 31%, which is not suitable for industrialization. The synthesis route is as follows:

[0008]

[0009] Method 3: CN111278812 reported that 2-chloro-4-trifluoromethylpyridine and 2-(2-hydroxyphenyl)acetic acid were reacted in DMF solution at 150 degrees under the action of potassium carbonate, and then acidified to obtain crude 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid with a yield of 84%. This intermediate was refluxed in methanol solvent under the action of methanesulfonic acid with a yield of 97%, and esterified to obtain 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid methyl ester, or 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid in DMF solution, potassium carbonate , dimethyl sulfate esterification with a yield of 95% to obtain 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid methyl ester, the esterification intermediate, titanium tetrachloride and methyl formate in a dichloromethane solution, formylation under the action of triethylamine to separate the organic layer to obtain (E)-3-hydroxy-2-[2-[[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]prop-2-enoic acid methyl ester, the organic layer with 10.6% sodium carbonate aqueous solution and dimethyl sulfate, phase transfer catalyst to obtain Flupyroxystrobin with a yield of 88%, the four-step comprehensive yield of 70%, the synthesis route is as follows:

[0010]

[0011] The raw materials of the third route are easily available and have a high yield, and are suitable for industrial production. However, in this process, highly toxic dimethyl sulfate is required for esterification and methylation, and titanium tetrachloride is used to catalyze the formylation of methyl formate. Titanium tetrachloride is a volatile liquid that produces hydrochloric acid mist when in contact with humid air, which is not easy to use industrially. 2-(2-hydroxyphenyl)acetic acid is prepared by chlorinating, cyaniding, and hydrolyzing ortho-chlorotoluene with chlorine gas, and then reacting with sodium hydroxide in the presence of 8-hydroxyquinoline copper (II) to obtain 2-(2-hydroxyphenyl)acetic acid, which has a price of 10w / t and is expensive. In addition, in the process of producing 2-(2-hydroxyphenyl)acetic acid, national key regulated hazardous chemical processes such as chlorination process and cyanidation process need to be used. These potential problems do not meet the current requirements for the development of green environmental protection. Now, there is an urgent need for a method for industrially producing Flupyroxystrobin with a simple synthesis process, easy operation, high safety factor, low cost, and simple synthesis process. Summary of the invention

[0012] Aiming at the shortcomings of the existing flupyroxystrobin synthesis process technology, the present invention provides a method for preparing flupyroxystrobin. 2-chloro-4-trifluoromethylpyridine and phenol are used as starting materials to carry out etherification reaction, condensation reduction reaction, formylation reaction and one-step alkylation to prepare flupyroxystrobin. The method has simple synthesis, easy operation, high safety factor, low cost and is suitable for industrial production.

[0013] The technical solution of the present invention is as follows:

[0014] A method for preparing Flupyroxystrobin, the reaction route is:

[0015]

[0016] Preferably, the reaction route can be:

[0017]

[0018] The specific steps are as follows:

[0019] (1) 2-Phenoxy-4-trifluoromethylpyridine is subjected to a condensation reaction with glyoxylic acid monohydrate and then subjected to a reduction reaction to obtain 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid.

[0020] (2) 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid is subjected to high pressure formylation reaction with carbon monoxide in a methanol solution containing sodium methoxide, the methanol is removed by decompression, a non-protonic polar solvent is added, and the mixture is alkylated with chloroform in the presence of an inorganic base to produce (2E)-3-methoxy-2-(2-{[4-(trifluoromethyl)-2-pyridyl]oxy}phenyl)acrylate.

[0021] The preparation method of 2-phenoxy-4-trifluoromethylpyridine described in step (1) can adopt the existing technology, preferably, the following method can be adopted: 2-chloro-4-trifluoromethylpyridine and phenol are used as starting materials for etherification reaction to obtain 2-phenoxy-4-trifluoromethylpyridine. The etherification reaction can be carried out according to the reaction conditions of the existing technology, specifically according to the preparation method disclosed in CN113773246A.

[0022] Preferably, in the condensation reaction in step (1), the solvent may be one of acetic acid and concentrated hydrochloric acid; preferably acetic acid.

[0023] Preferably, the condensation reaction in step (1) uses an acid as a catalyst, specifically one of concentrated hydrochloric acid, concentrated sulfuric acid, methanesulfonic acid, and trifluoromethanesulfonic acid; preferably methanesulfonic acid.

[0024] Preferably, in step (1), the reduction reaction uses phosphorous acid as a reducing agent, and the co-catalyst of the reduction reaction may be one of sodium iodide and potassium iodide.

[0025] Preferably, in step (1), the molar ratio of 2-phenoxy-4-trifluoromethylpyridine to glyoxylic acid monohydrate is 1:1-1:2; more preferably 1:2.

[0026] Preferably, the molar ratio of the condensation reaction catalyst to 2-phenoxy-4-trifluoromethylpyridine in step (1) is 1:1-3:1, and more preferably 1.8:1. Preferably, when the condensation reaction solvent and the catalyst in step (1) are both concentrated hydrochloric acid, the molar ratio of concentrated hydrochloric acid to 2-phenoxy-4-trifluoromethylpyridine is 20:1-25:1, and most preferably 22.9:1.

[0027] Preferably, in step (1), the molar ratio of the reducing agent to 2-phenoxy-4-trifluoromethylpyridine is 2:1-1:1; more preferably 2:1.

[0028] More preferably, the molar ratio of the co-catalyst for the reduction reaction in step (1) to 2-phenoxy-4-trifluoromethylpyridine is 0.1:1-1:1, more preferably 0.3:1.

[0029] Preferably, in step (1), the condensation reaction temperature is 40°C-70°C, more preferably 40°C-45°C; the reduction reaction temperature is 100°C-105°C.

[0030] Preferably, in the formylation reaction in step (2), the molar ratio of sodium methoxide to 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid is 1:1-2:1, more preferably 1.17:1. The mass ratio of methanol to 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid is 10:1-5:1, more preferably 9.9:1.

[0031] More preferably, in step (2), the carbon monoxide pressure in methanol is 4.25 MPa, and the formylation temperature is 50° C.-55° C.

[0032] Preferably, in the alkylation reaction of step (2), the solvent is one of DMF and DMAc; the inorganic base can be one of potassium carbonate, sodium carbonate, sodium hydroxide and potassium hydroxide, more preferably potassium carbonate.

[0033] Preferably, in the alkylation reaction of step (2), the alkylation temperature is 40°C-70°C, more preferably 45°C-50°C.

[0034] Preferably, in the alkylation reaction of step (2), the molar ratio of the base to 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid is 1:1-6:1, more preferably 5:1; the mass ratio of the solvent to 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid is 5:1-20:1, which can be 8:1, 10:1, 12:1, 15:1, 18:1, etc., and most preferably 7.4:1.

[0035] The beneficial effects of the present invention are:

[0036] The present invention provides a novel preparation method for synthesizing Flupyroxystrobin using 2-chloro-4-trifluoromethylpyridine, an inexpensive and readily available organic synthesis intermediate, as a starting material, and the reagents required in the reaction process are safe and readily available. In summary, compared with the prior art, the method provided by the present invention has undemanding reaction conditions, simple process, low cost, high yield, less three wastes, high safety, high production efficiency, and is green and environmentally friendly, and is suitable for large-scale industrial production. DETAILED DESCRIPTION

[0037] The present invention is further described by the following examples, but the following examples should not be construed as limiting the scope of protection of the present invention. Without departing from the technical scope of the present invention, any non-essential improvements and changes to the present invention should be included in the technical scope of the present invention.

[0038] The technical solution of this patent is further described in detail below in conjunction with specific implementation methods.

[0039] In the following examples, 2-phenoxy-4-trifluoromethylpyridine was synthesized according to the method of Example 4 of patent document CN113773246 A.

[0040] Example 1

[0041] (1) Synthesis of 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid

[0042] 2-Phenoxy-4-trifluoromethylpyridine (23.92 g, 0.1 mol, 1.0 eq), glyoxylic acid monohydrate (18.41 g, 0.2 mol, 2.0 eq) and acetic acid 170 g were added to a 1 L three-necked flask equipped with a magnet, a thermometer and a reflux condenser, and stirred to dissolve in an oil bath at 40°C to 45°C. Methanesulfonic acid (17.3 g, 0.18 mol, 1.8 eq) was added to the mixture and the temperature was kept at 40°C to 45°C. After reacting for 12.5 hours, the temperature was slowly lowered to room temperature, phosphorous acid (16.4 g, 0.2 mol, 2.0 eq) and sodium iodide (4.5 g, 30 mmol, 0.3 eq) were added, and the mixture was stirred in an oil bath at 100° C. to 105° C. for 3 hours, and then slowly cooled to room temperature. 170 g of distilled water was added, stirred, and allowed to stand to precipitate a brown solid, which was filtered and dried to obtain 26.2 g of 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid with a yield of 88.2%.

[0043] The obtained product was analyzed and the results are as follows:

[0044] 1 HNMR (400MHz, Chloroform-d) δ: 3.49 (s, 2H), 7.15 (d, 1H), 7.24 (t, 1H) 7.31-7.38 (m, 2H), 7.41 (d, 2H), 7.47 (d, 1H), 8.37 (d, 1H), 12.23 (s, 1H) ppm.

[0045] LC / MS: m / z=298.1 [M+H]+.

[0046] (2) Methyl (2E)-3-methoxy-2-(2-{[4-(trifluoromethyl)-2-pyridyl]oxy}phenyl)acrylate

[0047] In a 1L stainless steel autoclave, 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid (10.11 g, 34 mmol, 1.0 eq) prepared in step (1), methanol (100 g), and sodium methoxide (2.20 g, 40 mmol, 1.17 eq) were added, and carbon monoxide was introduced. The temperature was raised to 50°C to 55°C, and the carbon monoxide pressure was maintained at 4.25 MPa. The reaction was carried out for 6 hours, and the temperature was lowered and the pressure was released. The reaction solution was transferred to a single-mouth bottle, and the methanol was removed by decompression. 75 g of DMF was dissolved and the mixture was transferred to a 1L stainless steel autoclave. Powdered potassium carbonate (23.5 g, 0.17 mol, 5.0 eq) was added. After stirring at room temperature for 0.5 hour, methyl chloride gas was slowly introduced and the temperature was raised to 45°C-50°C for reaction until the reaction solution no longer absorbed methyl chloride and the reaction stopped. The temperature was slowly lowered to room temperature for decompression. 200 mL of distilled water and tert-butyl methyl ether (3x45 ml) were added and extracted three times. The organic phases were combined and washed with 100 ml of distilled water. The organic layer was separated and dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 11.05 g of methyl (2E)-3-methoxy-2-(2-{[4-(trifluoromethyl)-2-pyridyl]oxy}phenyl)acrylate, with a yield of 92%.

[0048] The obtained product was analyzed and the results are as follows:

[0049] 1 HNMR(400MHz,Chloroform-d)δ: 3.55(s,3H),3.70(s,3H),6.99(s,1H),7.12-7.20(m,2H)7.25-7.41(m,3H),7.42(s,2H),,8.32(d,1H)ppm.

[0050] LC / MS: m / z=354.3 [M+H]+.

[0051] Example 2

[0052] (1) Synthesis of 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid

[0053] 2-Phenoxy-4-trifluoromethylpyridine (23.92 g, 0.1 mol, 1.0 eq) (synthesized with reference to document CN113773246), glyoxylic acid monohydrate (13.8 g, 0.15 mol, 1.5 eq) and 170 g acetic acid were added to a 1 L three-necked flask equipped with a magnet, a thermometer and a reflux condenser, and stirred and dissolved in an oil bath at 40°C to 45°C. Concentrated sulfuric acid (10 g, 0.1 mol, 1.0 eq) was added to the mixture and the temperature was kept at 45°C. The reaction was continued at 50°C to 50°C for 16 hours, then slowly cooled to room temperature, phosphorous acid (16.4 g, 0.2 mol, 2.0 eq) and sodium iodide (4.5 g, 30 mmol, 0.3 eq) were added, and the mixture was stirred in an oil bath at 100°C to 105°C for 4 hours, then slowly cooled to room temperature, 170 g of distilled water was added, stirred and allowed to stand to precipitate a brown solid, which was filtered and dried to obtain 25.26 g of 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid with a yield of 85%.

[0054] (2) Synthesis of methyl (2E)-3-methoxy-2-(2-{[4-(trifluoromethyl)-2-pyridyl]oxy}phenyl)acrylate

[0055] In a 1L stainless steel autoclave, 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid (10.11 g, 34 mmol, 1.0 eq), methanol (100 g), and sodium methoxide (2.20 g, 40 mmol, 1.17 eq) prepared in step (1) were added. After carbon monoxide was introduced, the temperature was raised to 50°C to 55°C, the carbon monoxide pressure was maintained at 4.25 MPa, the reaction was continued for 6 hours, the temperature was lowered and the pressure was released, the reaction solution was transferred to a single-mouth bottle, the methanol was removed by decompression, 75 g of DMF was added, and the mixture was transferred to a 1L stainless steel autoclave after dissolution. Sodium carbonate (18.0 g, 0.17 mol, 5.0 eq) was added, and after stirring at room temperature for 1 hour, methyl chloride gas was slowly introduced, the temperature was raised to 60°C to 65°C, the reaction was continued until the reaction solution no longer absorbed methyl chloride, the reaction was stopped, the temperature was slowly lowered to room temperature and the pressure was released, 200 mL of distilled water and tert-butyl methyl ether (3 x 45 The organic phases were combined and washed with 100 ml of distilled water. The organic layer was separated and dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 10.21 g of methyl (2E)-3-methoxy-2-(2-{[4-(trifluoromethyl)-2-pyridyl]oxy}phenyl)acrylate. The yield was 85%.

[0056] Example 3

[0057] (1) Step A Synthesis of 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid

[0058] 2-Phenoxy-4-trifluoromethylpyridine (23.92 g, 0.1 mol, 1.0 eq) (synthesized with reference to document CN113773246), glyoxylic acid monohydrate (11.05 g, 0.12 mol, 0.12 eq) and 170 g of acetic acid were added to a 1 L three-necked flask equipped with a magnet, a thermometer and a reflux condenser, and stirred and dissolved in an oil bath at 40°C to 45°C. Methanesulfonic acid (17.3 g, 0.18 mol, 1.8 eq) was added to the mixture and the temperature was kept at The reaction was continued at 40°C to 45°C for 12.5 hours, then slowly cooled to room temperature, phosphorous acid (8.2 g, 0.1 mol, 1.0 eq) and potassium iodide (4.98 g, 30 mmol, 0.3 eq) were added, and the mixture was stirred in an oil bath at 100°C to 105°C for 3 hours, then slowly cooled to room temperature, 170 g of distilled water was added, stirred, and allowed to stand to precipitate a brown solid, which was filtered and dried to obtain 23.18 g of 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid with a yield of 78%.

[0059] (2) Synthesis of methyl (2E)-3-methoxy-2-(2-{[4-(trifluoromethyl)-2-pyridyl]oxy}phenyl)acrylate

[0060] In a 1L stainless steel autoclave, 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid (10.11 g, 34 mmol, 1.0 eq), methanol (100 g), and sodium methoxide (2.20 g, 40 mmol, 1.17 eq) prepared in step (1) were added. After carbon monoxide was introduced, the temperature was raised to 50°C to 55°C, the carbon monoxide pressure was maintained at 4.25 MPa, the reaction was carried out for 6 hours, the temperature was lowered and the pressure was released, the reaction solution was transferred to a single-mouth bottle, the methanol was removed by decompression, 95 g of DMF was added, and the mixture was transferred to a 1L stainless steel autoclave after dissolution, sodium hydroxide (3.13 g, 78 mmol, 2.3 eq) was added, and after stirring at room temperature for 1 hour, methyl chloride gas was slowly introduced, the temperature was raised to 55°C to 60°C for reaction, until the reaction solution no longer absorbed methyl chloride to stop the reaction, the temperature was slowly lowered to room temperature and the pressure was released, 200 mL of distilled water and tert-butyl methyl ether (3x45 The organic phases were combined and washed with 100 ml of distilled water. The organic layer was separated and dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 9.97 g of methyl (2E)-3-methoxy-2-(2-{[4-(trifluoromethyl)-2-pyridyl]oxy}phenyl)acrylate. The yield was 83%.

[0061] Example 4

[0062] (1) Step A Synthesis of 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid

[0063] 2-Phenoxy-4-trifluoromethylpyridine (23.92 g, 0.1 mol, 1.0 eq) (synthesized by referring to document CN113773246), glyoxylic acid monohydrate (9.2 g, 0.1 mol, 1.0 eq) and concentrated hydrochloric acid (220 g, 2.29 mol, 22.9 eq) were added to a 1 L three-necked flask equipped with a magnet, a thermometer and a reflux condenser. The reaction was continued at 60°C to 65°C for 20 hours. Then slowly cool to room temperature, add phosphorous acid (8.2 g, 0.1 mol, 1.0 eq) and sodium iodide (11.99 g, 80 mmol, 0.8 eq), stir in an oil bath at 100°C to 105°C for 6 hours, then slowly cool to room temperature, add 170 g of distilled water, stir and stand to precipitate a brown solid, filter and dry to obtain 22.30 g of 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid, with a yield of 75%.

[0064] (2) Synthesis of methyl (2E)-3-methoxy-2-(2-{[4-(trifluoromethyl)-2-pyridyl]oxy}phenyl)acrylate

[0065] In a 1L stainless steel autoclave, 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid (10.11 g, 34 mmol, 1.0 eq) prepared in step A of Example 4, methanol (80 g), and sodium methoxide (3.67 g, 68 mmol, 2.0 eq) were added, and carbon monoxide was introduced. The temperature was raised to 50°C to 55°C, and the carbon monoxide pressure was maintained at 4.25 MPa. The reaction was carried out for 8 hours, and the temperature was lowered and the pressure was released. The reaction solution was transferred to a single-mouth bottle, and the methanol was removed by decompression. 150 g DMAc was dissolved and the mixture was transferred to a 1L stainless steel autoclave. Powdered potassium carbonate (14.09 g, 0.102 mol, 3.0 eq) was added. After stirring at room temperature for 0.5 hour, methyl chloride gas was slowly introduced and the temperature was raised to 55°C-60°C for reaction until the reaction solution no longer absorbed methyl chloride and the reaction stopped. The temperature was slowly lowered to room temperature for decompression. 200 mL of distilled water and tert-butyl methyl ether (3x45 ml) were added and extracted three times. The organic phases were combined and washed with 100 ml of distilled water. The organic layer was separated and dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 9.61 g of methyl (2E)-3-methoxy-2-(2-{[4-(trifluoromethyl)-2-pyridyl]oxy}phenyl)acrylate, with a yield of 80%.

Claims

1. A method for preparing Flupyroxystrobin, characterized in that: The reaction route is:

2. The method for preparing Flupyroxystrobin according to claim 1, characterized in that: The reaction route is:

3. The method for preparing Flupyroxystrobin according to claim 1, characterized in that: The specific steps are as follows: (1) 2-phenoxy-4-trifluoromethylpyridine is subjected to a condensation reaction with glyoxylic acid monohydrate and then subjected to a reduction reaction to obtain 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid; (2) 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid is subjected to high pressure formylation reaction with carbon monoxide in a methanol solution containing sodium methoxide, the methanol is removed by decompression, a non-protonic polar solvent is added, and the mixture is alkylated with chloroform in the presence of an inorganic base to produce (2E)-3-methoxy-2-(2-{[4-(trifluoromethyl)-2-pyridyl]oxy}phenyl)acrylate.

4. The method for preparing Flupyroxystrobin according to claim 3, characterized in that: The preparation method of 2-phenoxy-4-trifluoromethylpyridine in step (1) is: 2-chloro-4-trifluoromethylpyridine and phenol are used as starting materials for etherification reaction to obtain 2-phenoxy-4-trifluoromethylpyridine.

5. The method for preparing Flupyroxystrobin according to claim 3, characterized in that: In the condensation reaction in step (1), the solvent can be one of acetic acid and concentrated hydrochloric acid; the condensation reaction in step (1) uses acid as a catalyst, specifically one of concentrated hydrochloric acid, concentrated sulfuric acid, methanesulfonic acid, and trifluoromethanesulfonic acid; the reduction reaction in step (1) uses a phosphorous acid reducing agent, and the co-catalyst of the reduction reaction is one of sodium iodide and potassium iodide.

6. The method for preparing Flupyroxystrobin according to claim 5, characterized in that: The molar ratio of 2-phenoxy-4-trifluoromethylpyridine to glyoxylic acid monohydrate in step (1) is 1:1-1:2; the molar ratio of the condensation reaction catalyst to 2-phenoxy-4-trifluoromethylpyridine in step (1) is 1:1-3:1; the molar ratio of the reducing agent to 2-phenoxy-4-trifluoromethylpyridine in step (1) is 2:1-1:1; the molar ratio of the reduction reaction promoter to 2-phenoxy-4-trifluoromethylpyridine in step (1) is 0.1:1-1:

1.

7. The method for preparing Flupyroxystrobin according to claim 5, characterized in that: When the condensation reaction solvent and the catalyst in step (1) are both concentrated hydrochloric acid, the molar ratio of concentrated hydrochloric acid to 2-phenoxy-4-trifluoromethylpyridine is 20:1-25:

1.

8. The method for preparing Flupyroxystrobin according to claim 3, characterized in that: In step (1), the condensation reaction temperature is 40°C-70°C; and the reduction reaction temperature is 100°C-105°C.

9. The method for preparing Flupyroxystrobin according to claim 3, characterized in that: In the formylation reaction in step (2), the molar ratio of sodium methoxide to 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid is 1:1-2:1; the mass ratio of methanol to 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid is 10:1-5:1; the carbon monoxide pressure in methanol in step (2) is 4.25 MPa; and the formylation temperature is 50°C-55°C.

10. The method for preparing Flupyroxystrobin according to claim 3, characterized in that: In the alkylation reaction of step (2), the solvent is one of DMF and DMAc; the inorganic base is one of potassium carbonate, sodium carbonate, sodium hydroxide and potassium hydroxide; in the alkylation reaction of step (2), the alkylation temperature is 40° C.-70° C.; in the alkylation reaction of step (2), the molar ratio of the base to 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid is 1:1-6:1; and the mass ratio of the solvent to 2-[2-[4-(trifluoromethyl)-2-pyridyl]oxy]phenyl]acetic acid is 5:1-20:1.

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