Preparation method of fluorine-containing pyrazole derivative
Through the steps of oxidation reaction, DAST reaction and hydrolysis reaction, the problem of using highly drugs and expensive raw materials in the synthesis of 3-difluoromethyl-1H-methylpyrazole-4-carboxylic acid in the prior art has been successfully solved, achieving high yield, low three waste and good industrial production value.
Patent Information
- Application Number
- CN202411649535.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-19
- Publication Date
- 2025-02-25
AI Technical Summary
In the prior art, highly drugs and expensive raw materials are used in the synthesis of 3-difluoromethyl-1H-methylpyrazole-4-carboxylic acid, and the yield is low and the three wastes are produced, which has safety and economic problems.
Using the steps of oxidation reaction, DAST reaction and hydrolysis reaction, 3-difluoromethyl-1H-methylpyrazole-4-carboxylic acid methyl ester reacts with an oxidant and a DAST reagent, and finally hydrolyzes in an alkaline aqueous solution to obtain 3-difluoromethyl-1H-methylpyrazole-4-carboxylic acid.
This method avoids the use of highly drugs, the raw materials are cheap and easy to obtain, the steps are simple, the yield is high, and the three wastes are less, and it has good industrial production value.
Smart Images
Figure CN119504588A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to the technical field of pesticide fungicide intermediate synthesis, in particular to a method for preparing a fluorine-containing pyrazole derivative. Background Art
[0002] 3-Difluoromethyl-1H-methylpyrazole-4-carboxylic acid (commonly known as difluoropyrazole acid) is mainly used in the production and preparation of a new generation of fungicides - SDHI fungicides. Succinate dehydrogenase (SDH) inhibitors mainly act on the electron transfer complex domain of the respiratory chain, blocking energy metabolism, inhibiting the growth of pathogens and leading to their death. Its representative drugs include sedaxane, benzovidiflupyr, bixafen, fluxapyroxad, and pyrazolaphthalamine. This type of fluorine-containing compound generally has the characteristics of good stability, rapid metabolism, and high lipid solubility in cells. 3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid is an important intermediate for the synthesis of difluoropyrazole carboxamide fungicides such as pyrazolaphthalamine.
[0003] The synthetic methods reported so far mainly include:
[0004] (1) The pyrazole ring is synthesized by using the pyrolysis product of 1,1,2,2-tetrafluoroethyl ether and ethyl dimethylaminoacrylate, and then using methylhydrazine as a raw material. This method is simple, but the temperature during the pyrolysis of tetrafluoroethyl ether is very high, which is relatively dangerous and has a low yield.
[0005] (2) Using ethyl difluoroacetate as the raw material, difluoropyrazole acid is obtained through condensation, cyclization and hydrolysis. Although the route is short, the fluorine-containing raw materials as starting materials are greatly affected by the market price. If the fluorine-containing raw materials cannot be self-sufficient, the profit will be greatly reduced.
[0006] (3) Synthesis using propargyl alcohol, sodium hypochlorite, acyl chloride, dimethylamine, difluoroacetic acid, and hydrazine hydrate as raw materials. This route uses cheap and readily available raw materials, has a high yield, and has mild reaction conditions. However, the raw material propargyl alcohol is highly toxic, the synthesis steps are long, and the three wastes generated are large and difficult to handle.
[0007] Therefore, there is an urgent need for a method for preparing a fluorine-containing pyrazole derivative to solve the above technical problems. Summary of the invention
[0008] The purpose of the present invention is to provide a method for synthesizing fluorine-containing pyrazole derivatives of pesticide fungicides, aiming at the fact that highly toxic substances are used in the synthesis process of 3-difluoromethyl-1H-methylpyrazole-4-carboxylic acid in the prior art, and the shortcomings of the prior art process such as expensive raw materials, low yield, and more three wastes. The raw materials used in the method are cheap and easily available, the steps are simple, the raw materials used are all non-toxic, the yield is high, and the method has good industrial production value.
[0009] To achieve the above object, the present invention is implemented according to the following technical solutions:
[0010] A method for preparing a fluorine-containing pyrazole derivative, wherein the fluorine-containing pyrazole derivative is 3-difluoromethyl-1H-methylpyrazole-4-carboxylic acid represented by formula (I);
[0011]
[0012] The preparation method comprises the following steps:
[0013] S1, oxidation reaction:
[0014] The 3-(hydroxymethyl)-1-methyl-1H-pyrazole-4-carboxylic acid methyl ester represented by formula (II) reacts with an oxidant in a first solvent to obtain the intermediate 3-formyl-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester represented by formula (III);
[0015]
[0016] S2, DAST reaction:
[0017] The intermediate 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester represented by formula (IV) is obtained by reacting a DAST reagent, a second solvent and the intermediate 3-formyl-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester represented by formula (III);
[0018]
[0019] S3, hydrolysis reaction:
[0020] The intermediate 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester represented by formula (IV) is hydrolyzed in an alkaline aqueous solution to obtain 3-difluoromethyl-1H-methylpyrazole-4-carboxylic acid represented by formula (I);
[0021]
[0022] Preferably, in step S1, the oxidant is at least one of potassium permanganate and manganese dioxide; and the molar ratio of the oxidant to ethyl 1-methyl-3-oxo-2,3-dihydropyrazole-4-carboxylate is 2 to 3:1.
[0023] Preferably, in step S1, the first solvent is dichloromethane.
[0024] Preferably, the reaction temperature of step S1 is room temperature, and the reaction time is 6 to 8 hours. Specifically, the room temperature is 25°C.
[0025] Further preferably, in step S1, the molar ratio of the oxidant to ethyl 1-methyl-3-oxo-2,3-dihydropyrazole-4-carboxylate is 2.2:1.
[0026] More preferably, in step S1, the oxidant is manganese dioxide.
[0027] Further preferably, in step S1, the reaction time is 6 hours.
[0028] Preferably, in step S2, the DAST reagent is diethylaminosulfur trifluoride, and the molar ratio of the DAST reagent to ethyl 3-formyl-1-methyl-1h-pyrazole-4-carboxylate is 1.2 to 1.5:1.
[0029] Preferably, in step S2, the second solvent is dichloromethane.
[0030] Preferably, in step S2, the reaction temperature is room temperature and the reaction time is 2 hours. Specifically, the room temperature is 25°C.
[0031] Further preferably, in step S2, the molar ratio of DAST reagent to ethyl 3-formyl-1-methyl-1h-pyrazole-4-carboxylate is 1.5:1.
[0032] Preferably, in step S3, the base in the alkaline aqueous solution is KOH or NaOH; and the molar ratio of the base in the alkaline aqueous solution to ethyl 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylate is 0.15 to 0.2:1.
[0033] Preferably, an organic solvent is also used in the hydrolysis process of step S3, and the amount of the organic solvent used is the same as the volume of the alkaline aqueous solution; the organic solvent is one of methanol, ethanol and tetrahydrofuran.
[0034] Specifically, the concentration of the alkaline aqueous solution is 15 M / L (mol / L).
[0035] Preferably, in step S3, the reaction temperature of the hydrolysis reaction is 25-40° C., and the reaction time is 8 hours.
[0036] More preferably, in step S3, the organic solvent is tetrahydrofuran.
[0037] Further preferably, in step S3, the base in the alkaline aqueous solution is NaOH.
[0038] Further preferably, in step S3, the molar ratio of the base in the alkaline aqueous solution to ethyl 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylate is 0.15:1.
[0039] Specifically, the step S1 is as follows:
[0040] Under nitrogen protection, dichloromethane, methyl 3-(hydroxymethyl)-1-methyl-1H-pyrazole-4-carboxylate and MnO2 were added to the reaction vessel, and the reaction was carried out at room temperature for 6 hours to obtain a reaction solution. The reaction solution was quenched with water, and the organic phase was extracted with dichloromethane. The organic phase was concentrated to obtain the intermediate 3-formyl-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester represented by formula (III).
[0041] Specifically, step S2 is as follows:
[0042] The intermediate 3-formyl-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester represented by formula (III) obtained in step S1 is dissolved in dichloromethane, diethylaminosulfur trifluoride is added, and the reaction is carried out at room temperature for 2 hours to obtain a reaction solution, the reaction solution is quenched with water, the organic phase is extracted with dichloromethane, and the organic phase is concentrated to obtain the intermediate 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester represented by formula (IV).
[0043] Specifically, step S3 is as follows:
[0044] The ethyl 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylate obtained in step S2 was dissolved in a 15M / L aqueous NaOH solution and an organic solvent THF, and the reaction was carried out at room temperature for 8 hours to obtain a reaction solution. The tetrahydrofuran in the reaction solution was evaporated to obtain an aqueous phase, and the pH of the aqueous phase was adjusted to 6 with HCl, and the mixture was filtered to obtain a white solid 3-difluoromethyl-1H-methylpyrazole-4-carboxylic acid.
[0045] Beneficial effects:
[0046] (1) The present invention provides a novel method for synthesizing 3-difluoromethyl-1H-methylpyrazole-4-carboxylic acid. DAST is used as a fluorination reagent during the reaction, and the synthesis method is simple.
[0047] (2) The present invention directly uses a reagent with a pyrazole ring, thereby avoiding the use of a highly toxic methylhydrazine in the ring-closing process. Methylhydrazine is a highly toxic substance that causes great harm to the environment and workers.
[0048] (3) The synthesis route adopted by the present invention is shorter, the yield is higher, and the three wastes are less. BRIEF DESCRIPTION OF THE DRAWINGS
[0049] Figure 1This is the NMR spectrum of the white solid 3-difluoromethyl-1H-methylpyrazole-4-carboxylic acid obtained in Example 1 of the present invention. DETAILED DESCRIPTION
[0050] The present invention is further described below with reference to specific embodiments. The illustrative embodiments and descriptions of the present invention are used to explain the present invention but are not intended to limit the present invention.
[0051] All raw materials of the present invention have no particular limitation on their sources, and can be purchased from the market or prepared according to conventional methods known to those skilled in the art.
[0052] There is no particular limitation on the purity of all raw materials in the present invention, and the present invention preferably adopts the conventional purity used in the art.
[0053] The devices used in the present invention are not particularly limited and can be any of the commonly used devices in the art.
[0054] Example 1
[0055] A method for preparing a fluorine-containing pyrazole derivative comprises the following steps:
[0056] S1, oxidation reaction:
[0057] Under nitrogen protection, 30 ml of dichloromethane, 9.2 g (0.05 mol) of methyl 3-(hydroxymethyl)-1-methyl-1H-pyrazole-4-carboxylate and 9.57 g (0.11 mol) of MnO2 were added to a 100 ml three-necked flask. After reacting for 6 h at room temperature (25 ° C), the reaction solution was quenched with water, the organic phase was extracted with dichloromethane, and the organic phase was concentrated to obtain 9 g (0.0495 mol) of the intermediate ethyl 3-formyl-1-methyl-1H-pyrazole-4-carboxylate (Formula III) with a purity of 98% and a yield of 99%.
[0058] S2, DAST reaction:
[0059] 9 g (0.0495 mol) of the intermediate 3-formyl-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (Formula III) was dissolved in 30 ml of dichloromethane, and 12 g (0.07 mol) of diethylaminosulfur trifluoride was added. After reacting for 2 h at room temperature (25°C), the reaction solution was quenched with water, and the organic phase was extracted with dichloromethane. After the organic phase was concentrated, 9.1 g (0.045 mol) of the intermediate 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (Formula IV) was obtained with a purity of 99% and a yield of 90%.
[0060] S3, hydrolysis reaction:
[0061] 9.1 g (0.045 mol) of the product of the previous step, 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (Formula IV), was dissolved in a mixture of 10 ml of a 15 M / L aqueous NaOH solution and 10 ml of an organic solvent, THF. After reacting for 8 h at room temperature (25° C.), the tetrahydrofuran in the reaction solution was evaporated, the pH of the aqueous phase was adjusted to 6 with HCl, and the mixture was filtered. The filter cake was 7.5 g (0.043 mol) of a white solid, 3-difluoromethyl-1H-methylpyrazole-4-carboxylic acid, with a purity of 99% and a yield of 95%.
[0062] like Figure 1 Shown is the NMR spectrum of the white solid 3-difluoromethyl-1H-methylpyrazole-4-carboxylic acid obtained in Example 1 of the present invention.
[0063] Example 2
[0064] A method for preparing a fluorine-containing pyrazole derivative comprises the following steps:
[0065] S1, oxidation reaction:
[0066] Under nitrogen protection, 30 ml of dichloromethane, 9.2 g (0.05 mol) of methyl 3-(hydroxymethyl)-1-methyl-1H-pyrazole-4-carboxylate, and 17.38 g (0.11 mol) of KMnO4 were added to a 100 ml three-necked flask. After reacting for 6 h at room temperature (25 ° C), the reaction solution was quenched with water, the organic phase was extracted with dichloromethane, and the organic phase was concentrated to obtain 8.64 g (0.0475 mol) of the intermediate 3-formyl-1-methyl-1h-pyrazole-4-carboxylic acid ethyl ester (Formula III) with a purity of 98% and a yield of 95%.
[0067] S2, DAST reaction:
[0068] 8.64 g (0.0475 mol) of the above intermediate 3-formyl-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (Formula III) was dissolved in 30 ml of dichloromethane, and 11.47 g (0.07 mol) of diethylaminosulfur trifluoride was added. After reacting for 2 hours at room temperature (25°C), the reaction solution was quenched with water, and the organic phase was extracted with dichloromethane. After the organic phase was concentrated, 7.75 g (0.038 mol) of the intermediate 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (Formula IV) was obtained with a purity of 95% and a yield of 80%.
[0069] S3, hydrolysis reaction:
[0070] 7.75 g (0.038 mol) of the product of the previous step, 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (Formula IV) was dissolved in a mixture of 10 ml of a 15 M / L aqueous solution of NaOH and 10 ml of an organic solvent, THF. After reacting for 8 h at room temperature (25° C.), the tetrahydrofuran in the reaction solution was evaporated, the pH of the aqueous phase was adjusted to 6 with HCl, and the mixture was filtered. The filter cake was 6.35 g (0.036 mol) of white solid 3-difluoromethyl-1H-methylpyrazole-4-carboxylic acid with a purity of 99% and a yield of 95%.
[0071] Example 3
[0072] A method for preparing a fluorine-containing pyrazole derivative comprises the following steps:
[0073] S1, oxidation reaction:
[0074] Under nitrogen protection, 30 ml of dichloromethane, 9.2 g (0.05 mol) of methyl 3-(hydroxymethyl)-1-methyl-1H-pyrazole-4-carboxylate, and 9.57 g (0.11 mol) of MnO were added to a 100 ml three-necked flask. 2， After reacting for 6 hours at room temperature (25°C), the reaction solution was quenched with water, the organic phase was extracted with dichloromethane, and the organic phase was concentrated to obtain 9 g (0.0495 mol) of the intermediate 3-formyl-1-methyl-1h-pyrazole-4-carboxylic acid ethyl ester (Formula III) with a purity of 98% and a yield of 99%.
[0075] S2, DAST reaction:
[0076] 9 g (0.0495 mol) of the intermediate 3-formyl-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (Formula III) was dissolved in 30 ml of dichloromethane, and 12 g (0.07 mol) of diethylaminosulfur trifluoride was added. After reacting for 2 h at room temperature (25°C), the reaction solution was quenched with water, and the organic phase was extracted with dichloromethane. After the organic phase was concentrated, 9.1 g (0.045 mol) of the intermediate 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (Formula IV) was obtained with a purity of 99% and a yield of 90%.
[0077] S3, hydrolysis reaction:
[0078] The product of the previous step, 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (Formula IV), 9.1 g (0.045 mol), was dissolved in 10 ml of 15 M / L NaOH aqueous solution. After reacting for 8 hours at room temperature (25°C), the pH of the aqueous phase was adjusted to 6 with HCl and filtered. The filter cake was 6.89 g (0.039 mol) of white solid 3-difluoromethyl-1H-methylpyrazole-4-carboxylic acid with a purity of 95% and a yield of 87%.
[0079] Example 4
[0080] A method for preparing a fluorine-containing pyrazole derivative comprises the following steps:
[0081] S1, oxidation reaction:
[0082] Under nitrogen protection, 30 ml of dichloromethane, 9.2 g (0.05 mol) of methyl 3-(hydroxymethyl)-1-methyl-1H-pyrazole-4-carboxylate, and 9.57 g (0.11 mol) of MnO were added to a 100 ml three-necked flask. 2， After reacting for 6 hours at room temperature (25°C), the reaction solution was quenched with water, the organic phase was extracted with dichloromethane, and the organic phase was concentrated to obtain 9 g (0.0495 mol) of the intermediate 3-formyl-1-methyl-1h-pyrazole-4-carboxylic acid ethyl ester (Formula III) with a purity of 98% and a yield of 99%.
[0083] S2, DAST reaction:
[0084] 9 g (0.0495 mol) of the intermediate 3-formyl-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (Formula III) was dissolved in 30 ml of dichloromethane, and 12 g (0.07 mol) of diethylaminosulfur trifluoride was added. After reacting for 2 h at room temperature (25°C), the reaction solution was quenched with water, and the organic phase was extracted with dichloromethane. After the organic phase was concentrated, 9.1 g (0.045 mol) of the intermediate 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (Formula IV) was obtained with a purity of 99% and a yield of 90%.
[0085] S3, hydrolysis reaction:
[0086] 9.1 g (0.045 mol) of the product of the previous step, 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (Formula IV) was dissolved in a mixture of 10 ml of a 15 M / L aqueous NaOH solution and 10 ml of an organic solvent, THF. After reacting at 40° C. for 8 h, the tetrahydrofuran in the reaction solution was evaporated, the pH of the aqueous phase was adjusted to 6 with HCl, and the reaction was filtered. The filter cake was 7.12 g (0.04 mol) of white solid 3-difluoromethyl-1H-methylpyrazole-4-carboxylic acid with a purity of 93% and a yield of 90%.
[0087] Comparative Example 1
[0088] Add 100 mL of ethyl acetate, 12.5 g (0.10 mol) of ethyl difluoroacetate, and 5.3 g (0.10 mol) of sodium ethoxide to a 250 mL three-necked flask, react at 30 ° C for 6 h, cool to room temperature (25 ° C), add 20.0 g (0.10 mol) of 98% concentrated sulfuric acid, filter, and distill under reduced pressure to obtain 10.5 g of ethyl 4,4-difluoroacetoacetate with a yield of 72.5% and a purity of 80%.
[0089] To a 100 mL single-mouth bottle, add 8.7 g (0.05 mol) of ethyl 4,4-difluoroacetoacetate, 41.5 g (0.40 mol) of acetic anhydride, and 14.9 g (0.1 mol) of triethyl orthoformate. React at 120°C for 12 hours. After the reaction, distill to obtain ethyl 2-ethoxymethylene-4,4-difluoroacetoacetate with a yield of 73.8% and a purity of 85.6%.
[0090] Add 4.7 g (0.02 mol) of ethyl 2-ethoxymethylene-4,4-difluoroacetoacetate, 40 mL of toluene, 4.3 g (0.03 mol) of methylhydrazine, and 2.4 g (0.06 mol) of sodium hydroxide to a 100 mL four-necked flask, and react at 90°C for 3 h. Extract and dry to obtain 3.8 g of ethyl 3-difluoromethyl-1-methylpyrazole-4-carboxylate, with a yield of 81.5% and a purity of 88.2%.
[0091] To a 100 mL reaction bottle, add 4.3 g (0.02 mol) of ethyl 3-difluoromethyl-1-methylpyrazole-4-carboxylate, 1.2 g (0.03 mol) of sodium hydroxide, and 30 mL of water. Stir at 60 ° C for 6 h. After the reaction, adjust the pH to 6 and filter to obtain 3.3 g of white solid 3-difluoromethyl-1H-methylpyrazole-4-carboxylic acid with a purity of 93% and a yield of 80%.
[0092] The technical solution of the present invention is not limited to the above-mentioned specific embodiments. All technical variations made according to the technical solution of the present invention fall within the protection scope of the present invention.
Claims
1. A method for preparing a fluorine-containing pyrazole derivative, characterized in that: The fluorine-containing pyrazole derivative is 3-difluoromethyl-1H-methylpyrazole-4-carboxylic acid represented by formula (I); the preparation method The following steps are involved: S1, oxidation reaction: The 3-(hydroxymethyl)-1-methyl-1H-pyrazole-4-carboxylic acid methyl ester represented by formula (II) reacts with an oxidant in a first solvent to obtain the intermediate 3-formyl-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester represented by formula (III); S2, DAST reaction: The intermediate 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester represented by formula (IV) is obtained by reacting a DAST reagent, a second solvent and the intermediate 3-formyl-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester represented by formula (III); S3, hydrolysis reaction: The intermediate 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester represented by formula (IV) is hydrolyzed in an alkaline aqueous solution to obtain 3-difluoromethyl-1H-methylpyrazole-4-carboxylic acid represented by formula (I); 2. The method for preparing a fluorine-containing pyrazole derivative according to claim 1, characterized in that: In the step S1, the oxidant is at least one of potassium permanganate and manganese dioxide; the molar ratio of the oxidant to 1-methyl-3-oxo-2,3-dihydropyrazole-4-carboxylic acid ethyl ester is 2 to 3:
1.
3. The method for preparing a fluorine-containing pyrazole derivative according to claim 1, characterized in that: In the step S1, the first solvent is dichloromethane.
4. The method for preparing a fluorine-containing pyrazole derivative according to claim 1, characterized in that: The reaction temperature of step S1 is room temperature, and the reaction time is 6 to 8 hours.
5. The method for preparing a fluorine-containing pyrazole derivative according to claim 1, characterized in that: In the step S2, the molar ratio of the DAST reagent to ethyl 3-formyl-1-methyl-1h-pyrazole-4-carboxylate is 1.2 to 1.5:
1.
6. The method for preparing a fluorine-containing pyrazole derivative according to claim 1, characterized in that: In the step S2, the second solvent is dichloromethane.
7. The method for preparing a fluorine-containing pyrazole derivative according to claim 1, characterized in that: In step S2, the reaction temperature is room temperature and the reaction time is 2 hours.
8. The method for preparing a fluorine-containing pyrazole derivative according to claim 1, characterized in that: In step S3, the base in the alkaline aqueous solution is KOH or NaOH; the molar ratio of the base in the alkaline aqueous solution to ethyl 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylate is 0.15-0.2:
1.
9. The method for preparing a fluorine-containing pyrazole derivative according to claim 1, characterized in that: An organic solvent is also used in the hydrolysis process of step S3, and the amount of the organic solvent used is the same as the volume of the alkaline aqueous solution; the organic solvent is tetrahydrofuran.
10. The method for preparing a fluorine-containing pyrazole derivative according to claim 1, characterized in that: In step S3, the reaction temperature of the hydrolysis reaction is 25-40° C., and the reaction time is 8 hours.