A process for the synthesis of isoxaflutole

Abstract

The present application relates to the technical field of heterocyclic compounds, and particularly relates to a synthesis process of isoxaflutole, which comprises the following steps: mixing raw materials, evaporating the solvent and low-boiling substances under reduced pressure after the mixing is completed to obtain an enol ether intermediate, dissolving the enol ether intermediate in ethanol, adding hydroxylamine hydrochloride and sodium acetate, evaporating the solvent under reduced pressure after the reaction is completed to obtain a ring closure intermediate, dissolving the ring closure intermediate in dichloromethane, adding meta-chloroperoxybenzoic acid in batches, and obtaining isoxaflutole after the reaction liquid is purified. The present application uses a solid catalyst in which phosphomolybdotungstic heteropoly acid is loaded on activated carbon to replace a traditional homogeneous oxidant. The loaded catalyst can effectively activate hydrogen peroxide, realize precise oxidation of a sulfide group (methylthio group) to a sulfone group (methylsulfonyl group), greatly reduce the risk of generation of by-products such as sulfoxide, and meanwhile, the reaction temperature is controlled at 55-60 DEG C, unnecessary side reactions caused by high-temperature oxidation are avoided, and the oxidation process is more moderate and controllable.

Description

Technical Field

[0001] This invention relates to the field of heterocyclic compound technology, and in particular to a synthetic process for isoxazolidinone. Background Technology

[0002] Isoxaflutole is a pre-emergence herbicide with systemic activity, enabling both soil and foliar application. Its unique mechanism of action involves inactive herbicide itself, acting as a "prodrug." Absorbed through the roots and leaves, it is transported throughout the plant and rapidly converted into a bioactive diketononitrile. This diketononitrile binds to HPPD (hydroxyphenylpyruvate dioxygenase), inhibiting the enzyme's oxidative decarboxylation of p-hydroxyphenylpyruvate. Due to the inhibition of carotenoid (protective photosynthesis) synthesis, poisoned weeds exhibit a whitening effect. Isoxaflutole demonstrates high efficiency and strong selectivity in controlling broadleaf weeds and some grassy weeds. Especially with the increasing demand for resistant weed control and the deepening of pesticide reduction and efficiency policies, it has become a key herbicide for weed control in field crops such as corn and soybeans, as well as specialty cash crops.

[0003] Traditional methods for preparing sulfone compounds by sulfide oxidation often employ catalyst-free or single-metal-salt catalysis, resulting in low hydrogen peroxide utilization and problems such as over-oxidation and incomplete reaction. This leads to low purity of intermediates, directly affecting the yield and quality of the final product. Therefore, to address the problems mentioned above, this invention proposes a synthetic process for isoxazolam. Summary of the Invention

[0004] The purpose of this invention is to provide a synthesis process for isoxazoline to solve the problems mentioned in the background art.

[0005] To achieve the above objectives, the present invention provides the following technical solution: a synthesis process for isoxazoline, comprising the following steps: S1. Mix 1-cyclopropyl-3-(2-methanesulfonyl-4-trifluoromethylphenyl)propane-1,3-dione, triethyl orthoformate, acetic anhydride and propionic acid solvent, and stir the mixture at 80-100℃ for 3-4 hours. After the reaction is completed, remove the solvent and low-boiling substances by vacuum distillation to obtain the enol ether intermediate.

[0006] S2. Dissolve the enol ether intermediate in ethanol, add hydroxylamine hydrochloride and sodium acetate, and reflux at 78-82℃ for 2-3 hours to cyclize. After the reaction is complete, remove the solvent by vacuum distillation, and wash the residue with water, extract and dry to obtain the cyclized intermediate.

[0007] S3. Dissolve the cyclized intermediate in dichloromethane, add m-chloroperoxybenzoic acid in batches at 0-5℃, stir at room temperature for 3-4 hours, and wash, dry and purify the reaction solution to obtain isoxazolidin.

[0008] 1-Cyclopropyl-3-(2-Methanesulfonyl-4-trifluoromethylphenyl)propane-1,3-dione is prepared by the following steps: S11. Mix 2-nitro-4-trifluoromethylbenzonitrile with toluene, add sodium methanethiol aqueous solution dropwise at room temperature, and stir the reaction at 40-50℃ for 2-4 hours after the addition is complete. Let stand and separate the liquids. The organic phase is washed with water, dried, filtered and concentrated to obtain 2-methylthio-4-trifluoromethylbenzonitrile.

[0009] S12. 2-Methylthio-4-trifluoromethylbenzonitrile, supported catalyst, anhydrous ethanol and hydrogen peroxide are stirred and mixed, and refluxed at 55-60℃ for 4-6 hours. After the reaction is completed, the reaction mixture is filtered, the filtrate is concentrated under reduced pressure, and anhydrous ethanol is added for recrystallization. The precipitated crystals are filtered, washed and dried to obtain 2-methanesulfonyl-4-trifluoromethylbenzonitrile.

[0010] S13. Dissolve 2-methanesulfonyl-4-trifluoromethylbenzonitrile and cyclopropylmethyl ketone in tetrahydrofuran to obtain solution A. Add potassium tert-butoxide to the tetrahydrofuran solution to obtain solution B. Add solution A dropwise to solution B while controlling the temperature at 0-5℃. After the addition is complete, keep warm and stir for 1-2 hours. After the reaction is completed, pour the reaction solution into an ice-water mixture, stir for 20-30 minutes, and then let it stand to separate the liquids. Wash the organic phase with water, dry it, and concentrate it to obtain 1-cyclopropyl-3-(2-methanesulfonyl-4-trifluoromethylphenyl)propane-1,3-dione.

[0011] As a preferred embodiment of the present invention, the supported catalyst in step S12 is prepared through the following steps: S121. Dissolve phosphomolybdenum tungsten heteropoly acid in ethanol, then add it dropwise to activated carbon powder while stirring. After all the powder has been added, a mixture is obtained.

[0012] S122. Let the mixture stand at room temperature for 20-24 hours, then vacuum dry the impregnated sample at 60-70℃ for 4-5 hours, and then activate it at 110-120℃ for 2-3 hours to obtain the supported catalyst.

[0013] As a preferred embodiment of the present invention, in step S1, the mass ratio of 1-cyclopropyl-3-(2-methanesulfonyl-4-trifluoromethylphenyl)propane-1,3-dione, triethyl orthoformate, acetic anhydride, and propionic acid is 1:(0.5-0.9):(0.05-0.15):(5-10).

[0014] As a preferred embodiment of the present invention, in step S2, the mass ratio of the enol ether intermediate, ethanol, hydroxylamine hydrochloride, and sodium acetate is 1:(3-8):(0.15-0.3):(0.2-0.5).

[0015] As a preferred embodiment of the present invention, the mass ratio of the cyclization intermediate, dichloromethane, and m-chloroperoxybenzoic acid in step S3 is 1:(8-16):(0.5-1.2).

[0016] The m-chloroperoxybenzoic acid was added in 3-5 portions, with an interval of 10-15 minutes between each addition.

[0017] As a preferred embodiment of the present invention, in step S11, the mass ratio of 2-nitro-4-trifluoromethylbenzonitrile, toluene, and sodium methanethiol aqueous solution is 1:(3-6):(1.5-2.5), wherein the mass fraction of sodium methanethiol aqueous solution is 15-20%.

[0018] As a preferred embodiment of the present invention, in step S12, the mass ratio of 2-methylthio-4-trifluoromethylbenzonitrile, supported catalyst, anhydrous ethanol and hydrogen peroxide is 1:(0.01-0.05):(4-8):(1-2.5).

[0019] The filtrate is concentrated under reduced pressure to 30-40% of its original volume, and the amount of anhydrous ethanol used is 2-3 times the volume of the concentrate.

[0020] As a preferred embodiment of the present invention, in step S13, the mass ratio of 2-methanesulfonyl-4-trifluoromethylbenzonitrile, cyclopropylmethyl ketone, and tetrahydrofuran in solution A is 1:(0.3-0.5):(5-10).

[0021] Solution B consists of potassium tert-butoxide and tetrahydrofuran in a mass ratio of 1:(5-10).

[0022] The mass ratio of solution A to solution B is 1:(1-1.5).

[0023] The mass ratio of the reaction solution to the ice-water mixture is 1:(3-5), and the pH of the ice-water mixture is adjusted to 1-2 using concentrated hydrochloric acid.

[0024] As a preferred embodiment of the present invention, the mass ratio of phospomolybdenum tungsten heteropoly acid, ethanol and activated carbon powder in step S121 is 1:(2-5):(1-3).

[0025] Compared with the prior art, the beneficial effects of the present invention are: 1. This invention uses a solid catalyst of phosphomolybdic tungsten heteropoly acid supported on activated carbon to replace the traditional homogeneous oxidant. This supported catalyst can effectively activate hydrogen peroxide and achieve precise oxidation of sulfone groups (methylthio groups) to sulfone groups (methanesulfonyl groups), which greatly reduces the risk of generating byproducts such as sulfoxide. At the same time, the reaction temperature is controlled at 55-60℃, avoiding unnecessary side reactions caused by high-temperature oxidation, making the oxidation process more mild and controllable.

[0026] 2. In this invention, the supported catalyst is a solid particle insoluble in the reaction system. After the reaction, it can be separated by simple filtration, facilitating catalyst recovery and reuse, and reducing production costs and waste liquid treatment burden. Furthermore, the entire synthesis route uses conventional solvents and common reagents, and the reaction conditions are mostly at atmospheric pressure and medium to low temperatures, ensuring good equipment compatibility and suitability for industrial-scale mass production. Attached Figure Description

[0027] Figure 1 This is a schematic diagram of the preparation process of isoxazoline in this invention; Figure 2 This is a schematic diagram of the preparation process of 1-cyclopropyl-3-(2-methanesulfonyl-4-trifluoromethylphenyl)propane-1,3-dione in this invention; Figure 3 This is a schematic diagram of the preparation process of the supported catalyst in this invention. Detailed Implementation

[0028] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0029] Please see Figures 1-3 This invention provides a technical solution for the synthesis of isoxazolidin: Example 1: A process for synthesizing isoxazoline includes the following steps: I. Preparation of supported catalysts: S121. Take 1.0g of phosphomolybdenum tungsten heteropoly acid, dissolve it in 2.0g of ethanol, add 1.0g of activated carbon powder, and stir until homogeneous to obtain a mixture.

[0030] S122. The mixture was allowed to stand at room temperature for 20 hours, dried under vacuum at 60°C for 4 hours, and activated at 110°C for 2 hours to obtain the supported catalyst.

[0031] II. Preparation of 1-cyclopropyl-3-(2-methanesulfonyl-4-trifluoromethylphenyl)propane-1,3-dione: S11. Mix 10.0g of 2-nitro-4-trifluoromethylbenzonitrile, 30.0g of toluene, and 15.0g of 15% sodium methanethiol aqueous solution, react at 40℃ for 2h, and then separate and dry to obtain 2-methylthio-4-trifluoromethylbenzonitrile.

[0032] S12. Mix 10.0g of 2-methylthio-4-trifluoromethylbenzonitrile, 0.1g of supported catalyst, 40.0g of anhydrous ethanol, and 10.0g of 30% hydrogen peroxide. Reflux at 55°C for 4h, concentrate to 30%, add 2 times the volume of ethanol for recrystallization, and obtain 2-methanesulfonyl-4-trifluoromethylbenzonitrile.

[0033] S13. Prepare solution A by mixing 10.0g of 2-methanesulfonyl-4-trifluoromethylbenzonitrile, 3.0g of cyclopropylmethyl ketone, and 50.0g of tetrahydrofuran; prepare solution B by mixing 10.0g of potassium tert-butoxide and 50.0g of tetrahydrofuran; add 10g of solution A dropwise to 10g of solution B (composed of potassium tert-butoxide and tetrahydrofuran in a mass ratio of 1:5) at 0℃, keep warm for 1h, pour in 3 times the mass of ice water (pH 1), stir for 20min, separate and dry to obtain 1-cyclopropyl-3-(2-methanesulfonyl-4-trifluoromethylphenyl)propane-1,3-dione.

[0034] III. Synthesis of isoxazolidin: S1. Mix 10.0g of 1-cyclopropyl-3-(2-methanesulfonyl-4-trifluoromethylphenyl)propane-1,3-dione, 5.0g of triethyl orthoformate, 0.5g of acetic anhydride, and 50.0g of propionic acid, react at 80℃ for 3h, and remove the solvent under reduced pressure to obtain an enol ether intermediate.

[0035] S2. Mix 10.0g of enol ether intermediate, 30.0g of ethanol, 1.5g of hydroxylamine hydrochloride and 2.0g of sodium acetate, reflux at 78°C for 2h, remove solvent, wash with water, extract with dichloromethane and dry to obtain isoxazole intermediate.

[0036] S3. Mix 10.0g of isoxazole intermediate and 80.0g of dichloromethane, add 5.0g of m-chloroperoxybenzoic acid in three portions at 0℃ (10min interval between each portion), react at room temperature for 3h, wash, dry and purify to obtain isoxazole oxadiazon.

[0037] Example 2: A process for synthesizing isoxazoline includes the following steps: I. Preparation of supported catalysts: S121. Take 1.0g of phosphomolybdenum tungsten heteropoly acid, dissolve it in 3.5g of ethanol, add 2.0g of activated carbon powder, and stir until homogeneous to obtain a mixture.

[0038] S122. The mixture was allowed to stand at room temperature for 22 hours, dried under vacuum at 65°C for 4.5 hours, and activated at 115°C for 2.5 hours to obtain the supported catalyst.

[0039] II. Preparation of 1-cyclopropyl-3-(2-methanesulfonyl-4-trifluoromethylphenyl)propane-1,3-dione: S11. Mix 10.0g of 2-nitro-4-trifluoromethylbenzonitrile, 45.0g of toluene, and 20.0g of 18% sodium methanethiol aqueous solution, react at 45℃ for 3h, and then separate and dry to obtain 2-methylthio-4-trifluoromethylbenzonitrile.

[0040] S12. Mix 10.0g of 2-methylthio-4-trifluoromethylbenzonitrile, 0.3g of supported catalyst, 60.0g of anhydrous ethanol and 18.0g of hydrogen peroxide, reflux at 58℃ for 5h, concentrate to 35%, add 2 times the volume of ethanol for recrystallization to obtain 2-methanesulfonyl-4-trifluoromethylbenzonitrile.

[0041] S13. Prepare solution A by mixing 10.0g of 2-methanesulfonyl-4-trifluoromethylbenzonitrile, 4.0g of cyclopropylmethyl ketone, and 80.0g of tetrahydrofuran; prepare solution B by mixing 10.0g of potassium tert-butoxide and 80.0g of tetrahydrofuran; add 10g of solution A dropwise to 13g of solution B (composed of potassium tert-butoxide and tetrahydrofuran in a mass ratio of 1:8) at 3℃, keep warm for 1.5h, pour in 4 times the mass of ice water (pH 1), stir for 25min, separate and dry to obtain 1-cyclopropyl-3-(2-methanesulfonyl-4-trifluoromethylphenyl)propane-1,3-dione.

[0042] III. Synthesis of isoxazolidin: S1. Mix 10.0g of 1-cyclopropyl-3-(2-methanesulfonyl-4-trifluoromethylphenyl)propane-1,3-dione, 7.0g of triethyl orthoformate, 1.0g of acetic anhydride, and 80.0g of propionic acid, react at 90℃ for 3.5h, and remove the solvent under reduced pressure to obtain an enol ether intermediate.

[0043] S2. Mix 10.0g of enol ether intermediate, 50.0g of ethanol, 2.2g of hydroxylamine hydrochloride and 3.5g of sodium acetate, reflux at 80℃ for 2.5h, remove solvent, wash with water, extract and dry to obtain isoxazole intermediate.

[0044] S3. Mix 10.0g of isoxazole intermediate and 120.0g of dichloromethane, add 9.0g of m-chloroperoxybenzoic acid in 4 portions at 2℃ (13min interval between each portion), react at room temperature for 3.5h, wash, dry and purify to obtain isoxazole oxadiazon.

[0045] Example 3: A process for synthesizing isoxazoline includes the following steps: I. Preparation of supported catalysts: S121. Take 1.0g of phosphomolybdenum tungsten heteropoly acid, dissolve it in 5.0g of ethanol, add 3.0g of activated carbon powder, and stir until homogeneous to obtain a mixture.

[0046] S122. The mixture was allowed to stand at room temperature for 24 hours, dried under vacuum at 70°C for 5 hours, and activated at 120°C for 3 hours to obtain the supported catalyst.

[0047] II. Preparation of 1-cyclopropyl-3-(2-methanesulfonyl-4-trifluoromethylphenyl)propane-1,3-dione: S11. Mix 10.0g of 2-nitro-4-trifluoromethylbenzonitrile, 60.0g of toluene, and 25.0g of 20% sodium methanethiol aqueous solution, react at 50℃ for 4h, and then separate and dry to obtain 2-methylthio-4-trifluoromethylbenzonitrile.

[0048] S12. Mix 10.0g of 2-methylthio-4-trifluoromethylbenzonitrile, 0.5g of supported catalyst, 80.0g of anhydrous ethanol and 25.0g of hydrogen peroxide, reflux at 60℃ for 6h, concentrate to 40%, add 3 times the volume of ethanol for recrystallization to obtain 2-methanesulfonyl-4-trifluoromethylbenzonitrile.

[0049] S13. Mix 10.0g of 2-methanesulfonyl-4-trifluoromethylbenzonitrile, 5.0g of cyclopropylmethyl ketone, and 100.0g of tetrahydrofuran to prepare solution A; mix 10.0g of potassium tert-butoxide and 100.0g of tetrahydrofuran to prepare solution B; add 10g of solution A dropwise to 15g of solution B (composed of potassium tert-butoxide and tetrahydrofuran in a mass ratio of 1:10) at 5℃, keep warm for 2h, pour in 5 times the mass of ice water (pH 2), stir for 30min, separate and dry to obtain 1-cyclopropyl-3-(2-methanesulfonyl-4-trifluoromethylphenyl)propane-1,3-dione.

[0050] III. Synthesis of isoxazolidin: S1. Mix 10.0g of 1-cyclopropyl-3-(2-methanesulfonyl-4-trifluoromethylphenyl)propane-1,3-dione, 9.0g of triethyl orthoformate, 1.5g of acetic anhydride, and 100.0g of propionic acid, react at 100℃ for 4h, and remove the solvent under reduced pressure to obtain an enol ether intermediate.

[0051] S2. Mix 10.0g of enol ether intermediate, 80.0g of ethanol, 3.0g of hydroxylamine hydrochloride and 5.0g of sodium acetate, reflux at 82℃ for 3h, remove solvent, wash with water, extract and dry to obtain isoxazole intermediate.

[0052] S3. Mix 10.0g of isoxazole intermediate and 160.0g of dichloromethane, add 12.0g of m-chloroperoxybenzoic acid in 5 portions at 5°C (15min interval between each portion), react at room temperature for 4h, wash, dry and purify to obtain isoxazole oxadiazon.

[0053] Comparative Example 1: Comparative Example 1 differs from Example 1 in that the supported catalyst is replaced with an equal mass of sodium tungstate, while the remaining steps are exactly the same as in Example 1.

[0054] Comparative Example 2: Comparative Example 2, compared to Example 1, did not add a supported catalyst, but the remaining steps were exactly the same as in Example 1.

[0055] Examples 1-3 and Comparative Examples 1-2 were used to prepare isoxazoline products. The following performance testing steps were used to evaluate the key quality indicators of each batch of products. The test items included: yield, liquid chromatography purity, and melting point.

[0056] I. Yield Calculation: Accurately weigh the final dried product of isoxazoline (in g), calculate the theoretical yield based on the mass of the starting material 2-nitro-4-trifluoromethylbenzonitrile according to the reaction equation, and calculate the yield using the following formula: Records: Actual yield, theoretical yield, and yield of each embodiment and comparative example.

[0057] II. Purity determination by high performance liquid chromatography (HPLC): 1. Solution preparation: Standard solution: Accurately weigh 10 mg of isoxaflutole standard, place it in a 25 mL volumetric flask, dissolve and dilute to the mark with acetonitrile, and shake well (concentration approximately 0.4 mg / mL).

[0058] Test solution: Weigh 10 mg of the samples from Examples 1-3 and Comparative Examples 1-2 respectively, and prepare them in the same way.

[0059] 2. Measurement steps: Inject the standard solution and the test solution into the liquid chromatograph separately. Chromatographic column: C18 reversed-phase column (4.6 mm × 250 mm, 5 μm), mobile phase: acetonitrile and water (volume ratio 60:40), flow rate: 1.0 mL / min, detection wavelength: 230 nm, column temperature: 30 ℃, injection volume: 10 μL. Record the chromatogram and calculate the chromatographic purity (%) of isoxaflutole in the test sample using the area normalization method.

[0060] Record: retention time of the main peak, percentage of peak area, and percentage of total impurity peak area for each sample.

[0061] III. Melting Point Determination: Preheat the capillary melting point apparatus to about 100°C. Take an appropriate amount of dry sample and put it into the capillary tube to a height of about 3-5 mm. Set the heating rate to 1-2°C / min. Observe and record the temperature range of initial melting (the sample begins to collapse and liquefy) and complete melting (completely turns into a transparent liquid). Record the melting point range (°C) of each sample. The specific test results are shown in Table 1.

[0062] Table 1: Performance Test Table of Isoxazolidin As shown in Table 1, the yields of Examples 1-3 ranged from 84.6% to 88.2%, and the chromatographic purity ranged from 97.8% to 98.9%. In contrast, Comparative Example 1 (using a homogeneous sodium tungstate catalyst) had a yield of only 72.3% and a purity of 94.5%; Comparative Example 2 (without catalyst) had an even lower yield of 58.7% and a purity of only 89.2%. This indicates that the phospomolybdenum-tungsten heteropolyacid supported catalyst used in this invention can efficiently and selectively catalyze the oxidation of sulfides to sulfone groups, significantly reducing... Fewer side reactions result in higher yields and purity of intermediates and final products. The melting point range of Examples 1-3 is concentrated in the range of 138-141℃ and the melting range is relatively narrow (2-3℃), which is consistent with the characteristics of high-purity isoxaflutole. In contrast, the melting range of Comparative Example 1 is slightly wider (136-140℃), and the melting point range of Comparative Example 2 is lower and the melting range is wider (134-138℃), indicating that it contains more impurities. This further confirms the problems of incomplete oxidation and increased by-products under catalyst deficiency or homogeneous catalytic systems.

[0063] The above are merely specific embodiments of the present invention, but the technical features of the present invention are not limited thereto. Any simple changes, equivalent substitutions, or modifications made based on the present invention to solve essentially the same technical problems and achieve essentially the same technical effects are all covered within the protection scope of the present invention.

Claims

1. A process for synthesizing isoxazolidin, characterized in that, Includes the following steps: S1. Mix 1-cyclopropyl-3-(2-methanesulfonyl-4-trifluoromethylphenyl)propane-1,3-dione, triethyl orthoformate, acetic anhydride and propionic acid solvent, and stir the reaction at 80-100℃ for 3-4 hours. After the reaction is completed, remove the solvent and low-boiling substances by vacuum distillation to obtain an enol ether intermediate. S2. Dissolve the enol ether intermediate in ethanol, add hydroxylamine hydrochloride and sodium acetate, and reflux at 78-82℃ for 2-3 hours to cyclize. After the reaction is complete, remove the solvent by vacuum distillation, and wash the residue with water, extract and dry to obtain the cyclized intermediate. S3. Dissolve the cyclized intermediate in dichloromethane, add m-chloroperoxybenzoic acid in portions at 0-5℃, stir at room temperature for 3-4 hours, wash, dry and purify the reaction solution to obtain isoxazolidin. 1-Cyclopropyl-3-(2-Methanesulfonyl-4-trifluoromethylphenyl)propane-1,3-dione is prepared by the following steps: S11. Mix 2-nitro-4-trifluoromethylbenzonitrile with toluene, add sodium methanethiol aqueous solution dropwise at room temperature, stir the reaction at 40-50℃ for 2-4 hours after the addition is complete, let stand and separate the liquids, and obtain 2-methylthio-4-trifluoromethylbenzonitrile after washing with water, drying, filtering and concentrating the organic phase. S12. 2-Methylthio-4-trifluoromethylbenzonitrile, supported catalyst, anhydrous ethanol and hydrogen peroxide are stirred and mixed, and refluxed at 55-60℃ for 4-6 hours. After the reaction is completed, the reaction mixture is filtered, the filtrate is concentrated under reduced pressure, and anhydrous ethanol is added for recrystallization. The precipitated crystals are filtered, washed and dried to obtain 2-methanesulfonyl-4-trifluoromethylbenzonitrile. S13. Dissolve 2-methanesulfonyl-4-trifluoromethylbenzonitrile and cyclopropylmethyl ketone in tetrahydrofuran to obtain solution A. Add potassium tert-butoxide to the tetrahydrofuran solution to obtain solution B. Add solution A dropwise to solution B while controlling the temperature at 0-5℃. After the addition is complete, keep warm and stir for 1-2 hours. After the reaction is completed, pour the reaction solution into an ice-water mixture, stir for 20-30 minutes, and then let it stand to separate the liquids. Wash the organic phase with water, dry it, and concentrate it to obtain 1-cyclopropyl-3-(2-methanesulfonyl-4-trifluoromethylphenyl)propane-1,3-dione.

2. The synthesis process of isoxazolidin according to claim 1, characterized in that: The supported catalyst in step S12 is prepared through the following steps: S121. Dissolve phosphomolybdenum tungsten heteropoly acid in ethanol, then add it dropwise to activated carbon powder while stirring. After all the powder has been added, a mixture is obtained. S122. Let the mixture stand at room temperature for 20-24 hours, then vacuum dry the impregnated sample at 60-70℃ for 4-5 hours, and then activate it at 110-120℃ for 2-3 hours to obtain the supported catalyst.

3. The synthesis process of isoxazolidin according to claim 1, characterized in that: In step S1, the mass ratio of 1-cyclopropyl-3-(2-methanesulfonyl-4-trifluoromethylphenyl)propane-1,3-dione, triethyl orthoformate, acetic anhydride, and propionic acid is 1:(0.5-0.9):(0.05-0.15):(5-10).

4. The synthesis process of isoxazolidin according to claim 1, characterized in that: In step S2, the mass ratio of the enol ether intermediate, ethanol, hydroxylamine hydrochloride, and sodium acetate is 1:(3-8):(0.15-0.3):(0.2-0.5).

5. The synthesis process of isoxazolidin according to claim 1, characterized in that: In step S3, the mass ratio of the cyclization intermediate, dichloromethane, and m-chloroperoxybenzoic acid is 1:(8-16):(0.5-1.2). The m-chloroperoxybenzoic acid was added in 3-5 portions, with an interval of 10-15 minutes between each addition.

6. The synthesis process of isoxazolidin according to claim 1, characterized in that: In step S11, the mass ratio of 2-nitro-4-trifluoromethylbenzonitrile, toluene, and sodium methanethiol aqueous solution is 1:(3-6):(1.5-2.5), wherein the mass fraction of sodium methanethiol aqueous solution is 15-20%.

7. The synthesis process of isoxazolidin according to claim 1, characterized in that: In step S12, the mass ratio of 2-methylthio-4-trifluoromethylbenzonitrile, supported catalyst, anhydrous ethanol, and hydrogen peroxide is 1:(0.01-0.05):(4-8):(1-2.5). The filtrate is concentrated under reduced pressure to 30-40% of its original volume, and the amount of anhydrous ethanol used is 2-3 times the volume of the concentrate.

8. The synthesis process of isoxazolidin according to claim 1, characterized in that: In step S13, the mass ratio of 2-methanesulfonyl-4-trifluoromethylbenzonitrile, cyclopropyl methyl ketone, and tetrahydrofuran in solution A is 1:(0.3-0.5):(5-10). Solution B consists of potassium tert-butoxide and tetrahydrofuran in a mass ratio of 1:(5-10); The mass ratio of solution A to solution B is 1:(1-1.5); The mass ratio of the reaction solution to the ice-water mixture is 1:(3-5), and the pH of the ice-water mixture is adjusted to 1-2 using concentrated hydrochloric acid.

9. The synthesis process of isoxazolidin according to claim 2, characterized in that: In step S121, the mass ratio of phospomolybdenum tungsten heteropoly acid, ethanol, and activated carbon powder is 1:(2-5):(1-3).

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