A process for the preparation of 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride

Abstract

The application provides a preparation method of 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride, which comprises the following steps: S1: 2-acetyl-3-chloro-5-trifluoromethylpyridine is reacted with hydroxylamine and p-toluenesulfonyl chloride under alkaline conditions in a solution to obtain 1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethylamino p-toluenesulfonate; S2: 1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethylamino p-toluenesulfonate is reacted under alkaline conditions at low temperature in a solution to obtain 2-amino-1-(3-chloro-5-trifluoromethylpyridin-2-yl)ethanone; S3: 2-amino-1-(3-chloro-5-trifluoromethylpyridin-2-yl)ethanone is reduced by a reducing agent under the action of a catalyst in a solution, and finally salification is carried out to obtain 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride. The application has the beneficial effects that the total yield of three steps is 82%, the product purity is greater than 99%, the solvent can be recycled and reused, the reaction route is short, the reaction yield is high, the product purity is high, no special process is needed, and the application can be popularized in industry.

Description

Technical Field

[0001] This invention belongs to the fields of organic synthesis and fine chemicals, and in particular relates to a method for preparing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride, an intermediate of fluopyramid. Background Technology

[0002] Fluopyram is a pyridine ethyl benzamide fungicide discovered and developed by Bayer and first reported in 2009. In 2003, Bayer Crop Science applied for a compound patent for fluopyram, and the compound patent protection in China is valid until August 7, 2023.

[0003] Currently, the main methods for synthesizing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride in the literature are:

[0004] Patent document WO2004016088 uses 2,3-dichloro-5-trifluoromethylpyridine and ethyl cyanoacetate as starting materials to produce 2-ethylamino-3-chloro-5-trifluoromethylpyridine hydrochloride through a four-step chemical reaction. The reaction route is lengthy, and the incomplete reduction and hydrolysis of the cyano group easily generates impurities that are difficult to remove, resulting in a product quality below 95%. The above reaction formula is:

[0005] Summary of the Invention

[0006] In view of this, the present invention aims to provide a method for preparing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride, which has a simple preparation process, high reaction yield, and high product purity.

[0007] To achieve the above objectives, the technical solution of the present invention is implemented as follows:

[0008] A method for preparing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride includes the following steps: S1: 2-acetyl-3-chloro-5-trifluoromethylpyridine and hydroxylamine react with p-toluenesulfonyl chloride in solution under alkaline conditions to obtain 1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethylamino-p-toluenesulfonate;

[0009] S2: 1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethylamino-p-toluenesulfonate reacts in solution at low temperature under alkaline conditions to give 2-amino-1-(3-chloro-5-trifluoromethylpyridin-2-yl)ethyl ketone;

[0010] S3: 2-Amino-1-(3-chloro-5-trifluoromethylpyridin-2-yl)acetone is reduced in solution by a reducing agent under the action of a catalyst, finally forming a salt to give 2-aminoethyl-3-chloro-5-trifluoromethylpyridinium hydrochloride.

[0011] The reaction formulas for the above three steps are:

[0012]

[0013] Step S1 further includes 2-acetyl-3-chloro-5-trifluoromethylpyridine and hydroxylamine, which are stirred with the first-stage alkaline substance in the first-stage solvent at room temperature for a period of time, heated to reflux reaction, filtered, and the filter cake is washed with water to obtain 1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethanol oxime. The second-stage solvent and the second-stage alkaline substance are added, and after the reaction with p-toluenesulfonyl chloride is completed under heating conditions, water is added, the solvent is recovered from the organic phase, cooled, filtered, and vacuum dried to obtain 1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethylamino-p-toluenesulfonate.

[0014] Step S2 further includes the 1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethylamino-p-toluenesulfonate obtained in step S1, which is cooled in a solvent and reacted with an alkaline substance. After the reaction is complete, dichloromethane is added, the organic phase is washed with an aqueous acetic acid solution, the solvent is recovered, and the product is cooled, filtered, and vacuum dried to obtain 2-amino-1-(3-chloro-5-trifluoromethylpyridin-2-yl)ethyl ketone.

[0015] Step S3 further includes reacting the 2-amino-1-(3-chloro-5-trifluoromethylpyridin-2-yl) ethyl ketone obtained in step S2 with a reducing agent in a solvent at a certain temperature in the presence of a catalyst until complete, adding sodium bisulfate aqueous solution and ethyl acetate dropwise, taking the organic phase, adding hydrochloric acid, and filtering to obtain 2-aminoethyl-3-chloro-5-trifluoromethylpyridinium hydrochloride.

[0016] The hydroxylamine in step S1 includes one of hydroxylamine hydrochloride, hydroxylamine sulfate, hydroxylamine aqueous solution, hydroxylamine nitrate, and hydroxylamine phosphate. Preferably, the hydroxylamine is hydroxylamine hydrochloride.

[0017] The solvents in the first and second stages of step S1 include one or more of alcohols, esters, haloalkanes, ethers, and amides.

[0018] The solvent for the first stage is preferably an alcohol, and more preferably an aqueous ethanol solution;

[0019] The solvent for the second stage is preferably a haloalkane, and more preferably dichloromethane.

[0020] The alkaline substances in the first and second stages of step S1 include one or more of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, triethylamine, isopropylamine, and methylamine aqueous solution. Preferably, the alkaline substance in the first stage is sodium hydroxide; the alkaline substance in the second stage is methylamine aqueous solution, preferably a 40% methylamine solution.

[0021] The molar ratio of raw materials in step S1 is as follows: 2-acetyl-3-chloro-5-trifluoromethylpyridine: hydroxylamine: first-stage alkaline substance: first-stage solvent: p-toluenesulfonyl chloride: second-stage alkaline substance: second-stage solvent = 1:(1-2):(1-2):(20-40):(1-1.5):(1-1.5):(30-50);

[0022] The optimal ratio is: 2-acetyl-3-chloro-5-trifluoromethylpyridine: hydroxylamine: sodium hydroxide: ethanol / water: p-toluenesulfonyl chloride: methylamine aqueous solution: second-stage solvent = 1:1.5:1.6:30:1.2:1.3:41;

[0023] In step S2, the solvent includes one or two of methanol, ethanol, isopropanol, butanol, dichloromethane, ethyl acetate, and dimethylacetamide; preferably, the solvent is isopropanol.

[0024] The alkaline substance in step S2 includes one or two of sodium hydroxide, potassium hydroxide, sodium ethoxide, potassium ethoxide, sodium isopropoxide, and potassium isopropoxide.

[0025] Preferably, the alkaline substance is potassium isopropoxide;

[0026] In step S2, the temperature is lowered to -5°C in the solvent;

[0027] In step S2, the molar ratio of raw materials is: 1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethylamino-p-toluenesulfonate: basic substance: solvent = 1:(1-2):(15-30), and the preferred ratio is 1:1.5:20.

[0028] The solvent in step S3 includes one or more of diethyl ether, tetrahydrofuran, dichloromethane, chloroform, dichloroethane, and toluene, preferably dichloromethane.

[0029] The reducing agent in step S3 includes one or more of sodium borohydride, lithium aluminum hydride, trimethylchlorosilane, hydrogen, and zinc amalgam. Preferably, the reducing agent is trimethylchlorosilane.

[0030] In step S3, the catalyst includes one of trifluoroacetic acid, acetic acid, palladium on carbon, acetic anhydride, trifluoropropionic acid, boron trifluoride diethyl ether, boron trifluoride butyl ether, etc., preferably boron trifluoride diethyl ether.

[0031] In step S3, the molar ratio of the raw materials is: 2-amino-1-(3-chloro-5-trifluoromethylpyridin-2-yl) acetone: trimethylchlorosilane: boron trifluoride ether: solvent = 1:(1-5):(1-4):(20-40); preferably, 2-amino-1-(3-chloro-5-trifluoromethylpyridin-2-yl) acetone: trimethylchlorosilane: boron trifluoride ether: solvent = 1:3:2:30;

[0032] Preferably, in step S4, 2-amino-1-(3-chloro-5-trifluoromethylpyridin-2-yl)ethyl ketone reacts completely with a reducing agent in a solvent at 10-25°C in the presence of a catalyst.

[0033] Compared with the prior art, the preparation method of 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride according to the present invention has the following advantages:

[0034] This invention provides a novel method for synthesizing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride, an intermediate of fluopyram. The route uses commercially available 2-acetyl-3-chloro-5-trifluoromethylpyridine as a raw material, and proceeds through a three-step reaction with an overall yield of 82% and a product purity greater than 99%. The solvent used is recyclable, the reaction route is short, the reaction yield is high, the product purity is high, no special processes are required, and it can be industrially promoted. Detailed Implementation

[0035] It should be noted that, unless otherwise specified, the embodiments and features described in the present invention can be combined with each other.

[0036] The present invention will now be described in detail with reference to embodiments.

[0037] Example 1

[0038] Step 1: At room temperature, add 22.3g of 2-acetyl-3-chloro-5-trifluoromethylpyridine, 10.4g of hydroxylamine hydrochloride, and 156g of 90% ethanol aqueous solution to a reaction flask. Then, add 6.4g of sodium hydroxide in two batches. After stirring at room temperature for 1 hour, heat to reflux to react, and a white solid precipitates. Filter, and the filtrate can be recycled. The filter cake was washed with water and rinsed with 50% ethanol-water mixture. The mixture was then dried to obtain 1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethanol oxime, which was directly added to a three-necked flask. 350 g of dichloromethane and 10.3 g of 40% methylamine aqueous solution were added. The mixture was heated to 50°C, and 22.8 g of p-toluenesulfonyl chloride was added in two batches. After the reaction was complete, 300 ml of water was added, and the mixture was allowed to separate into layers. The layers were washed three times with 100 ml of water. The organic phase was collected, and 50% of the solvent was recovered. The mixture was cooled to 0°C, and a solid precipitated. After stirring for 1 hour, the mixture was filtered, and the filter cake was washed with a small amount of solvent. The mixture was then dried under vacuum to obtain 37.9 g of 1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethylamino-p-toluenesulfonate, with a yield of 96.68%.

[0039] Step 2: 35g of 1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethylamino-p-toluenesulfonate was added to a three-necked flask, followed by 107g of isopropanol. The mixture was cooled to -5°C, and 13g of potassium isopropoxide was added in three batches, maintaining the reaction temperature below 10°C. After the reaction was complete, 500ml of dichloromethane was added to the reaction solution. After stirring for 1 hour, the mixture separated into layers. The dichloromethane layer was collected and washed twice with 100ml of 10% acetic acid aqueous solution. The organic phase was dried over anhydrous magnesium sulfate, filtered, and 50% of the solvent was distilled off. The mixture was then cooled, filtered, and dried under vacuum to obtain 19.5g of 2-amino-1-(3-chloro-5-trifluoromethylpyridin-2-yl)acetone, with a yield of 91.85%.

[0040] Step 3: 19g of 2-amino-1-(3-chloro-5-trifluoromethylpyridin-2-yl)acetone was added to a three-necked flask, along with 200g of dichloromethane and 27.9g of trimethylchlorosilane. 22.7g of boron trifluoride diethyl ether solution was added dropwise at 10-25℃. After the addition was complete, the reaction was maintained at this temperature until the reactants were fully reacted. Then, 50g of 10% sodium bisulfate aqueous solution was added dropwise. After the addition was complete, 400ml of ethyl acetate was added to extract the organic phase. 20ml of hydrochloric acid was then added, and the mixture was filtered and washed with ethyl acetate. 19.3g of 2-aminoethyl-3-chloro-5-trifluoromethylpyridinium hydrochloride was obtained, yielding 92.34% and a liquid phase purity of 99.57%.

[0041] Example 2

[0042] Step 1: At room temperature, add 22.3g of 2-acetyl-3-chloro-5-trifluoromethylpyridine, 13.8g of hydroxylamine hydrochloride, and 173g of 90% ethanol aqueous solution to a reaction flask. Then, add 8g of sodium hydroxide in two batches. After stirring at room temperature for 1 hour, the mixture is heated to reflux, and a white solid precipitates. Filter the solution, and the filtrate can be recycled. The filter cake was washed with water and rinsed with 50% ethanol-water mixture. The mixture was then dried to obtain 1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethanol oxime, which was directly added to a three-necked flask. 350 g of dichloromethane and 12 g of 40% methylamine aqueous solution were added. The mixture was heated to 50°C, and 20.9 g of p-toluenesulfonyl chloride was added in two batches. After the reaction was complete, 300 ml of water was added, and the mixture was allowed to separate into layers. The layers were washed three times with 100 ml of water. The organic phase was collected, and 50% of the solvent was recovered. The mixture was cooled to 0°C, and a solid precipitated. After stirring for 1 hour, the mixture was filtered, and the filter cake was washed with a small amount of solvent. The mixture was then dried under vacuum to obtain 36.9 g of 1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethylamino-p-toluenesulfonate, with a yield of 94.13%.

[0043] Step 2: 35g of 1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethylamino-p-toluenesulfonate was added to a three-necked flask, followed by 140g of isopropanol. The mixture was cooled to -5°C, and 18g of potassium isopropoxide was added in three batches, maintaining the reaction temperature below 10°C. After the reaction was complete, 500ml of dichloromethane was added to the reaction solution. After stirring for 1 hour, the mixture separated into layers. The dichloromethane layer was collected and washed twice with 130ml of 10% acetic acid aqueous solution. The organic phase was dried over anhydrous magnesium sulfate, filtered, and 50% of the solvent was distilled off. The mixture was then cooled, filtered, and dried under vacuum to obtain 18.7g of 2-amino-1-(3-chloro-5-trifluoromethylpyridin-2-yl)acetone, with a yield of 88.08%.

[0044] Step 3: 18g of 2-amino-1-(3-chloro-5-trifluoromethylpyridin-2-yl)acetone was added to a three-necked flask, along with 190g of dichloromethane and 26g of trimethylchlorosilane. 34g of boron trifluoride diethyl ether solution was added dropwise at 10-25℃. After the addition was complete, the reaction was maintained at this temperature until the reactants were fully reacted. Then, 63g of 10% sodium bisulfate aqueous solution was added dropwise. After the addition was complete, 350ml of ethyl acetate was added to extract the organic phase. 18ml of hydrochloric acid was then added, and the mixture was filtered and washed with ethyl acetate. 18.6g of 2-aminoethyl-3-chloro-5-trifluoromethylpyridinium hydrochloride was obtained, yielding 88.57% and a liquid phase purity of 99.12%.

[0045] Example 3

[0046] Step 1: At room temperature, add 22.3g of 2-acetyl-3-chloro-5-trifluoromethylpyridine, 14.5g of hydroxylamine nitrate, and 180g of 90% ethanol aqueous solution to a reaction flask. Then, add 8g of sodium hydroxide in two batches. After stirring at room temperature for 1 hour, the mixture is heated to reflux, and a white solid precipitates. Filter the solution, and the filtrate can be recycled. The filter cake was washed with water and rinsed with 50% ethanol-water mixture. The mixture was then dried to obtain 1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethanol oxime, which was directly added to a three-necked flask. 400 g of dichloromethane and 11 g of 40% methylamine aqueous solution were added. The mixture was heated to 50°C, and 21 g of p-toluenesulfonyl chloride was added in two batches. After the reaction was complete, 300 ml of water was added. The mixture was divided into portions, washed three times with 100 ml of water, and the organic phase was collected. 50% of the solvent was recovered. The mixture was cooled to 0°C, and a solid precipitated. After stirring for 1 hour, the mixture was filtered, and the filter cake was washed with a small amount of solvent. The mixture was then dried under vacuum to obtain 36.8 g of 1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethylamino-p-toluenesulfonate, with a yield of 93.87%.

[0047] Step 2: 35g of 1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethylamino-p-toluenesulfonate was added to a three-necked flask, followed by 107g of ethanol. The mixture was cooled to -5°C, and 12g of potassium ethoxide was added in three batches, maintaining the reaction temperature below 5°C. After the reaction was complete, 500ml of dichloromethane was added to the reaction solution, and the mixture was stirred for 1 hour. The layers separated, and the dichloromethane layer was collected and washed twice with 100ml of 10% acetic acid aqueous solution. The organic phase was dried over anhydrous magnesium sulfate, filtered, and 50% of the solvent was distilled off. The mixture was then cooled, filtered, and dried under vacuum to obtain 16.4g of 2-amino-1-(3-chloro-5-trifluoromethylpyridin-2-yl)acetone, with a yield of 77.25%.

[0048] Step 3: Add 80g of tetrahydrofuran to a three-necked flask, cool to 0℃ in an ice bath, add 4g of lithium aluminum hydride, and add 16g of 2-amino-1-(3-chloro-5-trifluoromethylpyridin-2-yl)ethyl ketone in four batches to the reaction solution. Maintain the reaction temperature not exceeding 5℃ until the reactants have reacted completely. Add the reaction solution dropwise to 500 mL of ice water. After the addition is complete, filter, add the filter cake to 50 mL of ethyl acetate, add 9g of hydrochloric acid, stir at below 10℃ for 2 hours, and filter to obtain 12.5g of 2-aminoethyl-3-chloro-5-trifluoromethylpyridinium hydrochloride, with a yield of 71.47% and a liquid phase purity of 98.35%.

[0049] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride, characterized in that: Step S1: 2-Acetyl-3-chloro-5-trifluoromethylpyridine and hydroxylamine are stirred with the first-stage alkaline substance in the first-stage solvent at room temperature for a period of time, then heated to reflux reaction, filtered, the filter cake is washed with water, and rinsing is used to obtain 1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethanol oxime, the second-stage solvent and the second-stage alkaline substance are added, and after the reaction with p-toluenesulfonyl chloride is completed under heating conditions, water is added, the solvent is recovered from the organic phase, cooled, filtered and vacuum dried to obtain 1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethylamino-p-toluenesulfonate; The alkaline substance in the first stage is sodium hydroxide; the alkaline substance in the second stage is an aqueous solution of methylamine. Step S2: The 1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethylamino-p-toluenesulfonate obtained in step S1 is cooled in a solvent and reacted with an alkaline substance. After the reaction is complete, dichloromethane is added, the organic phase is washed with an aqueous acetic acid solution, the solvent is recovered, and the mixture is cooled, filtered, and vacuum dried to obtain 2-amino-1-(3-chloro-5-trifluoromethylpyridin-2-yl)ethyl ketone. In step S2, the temperature is lowered to -5°C in the solvent; Step S3: The 2-amino-1-(3-chloro-5-trifluoromethylpyridin-2-yl) ethyl ketone obtained in step S2 reacts completely with a reducing agent in a solvent at a certain temperature in the presence of a catalyst. Sodium bisulfate aqueous solution and ethyl acetate are added dropwise, and hydrochloric acid is added to the organic phase. After filtration, 2-aminoethyl-3-chloro-5-trifluoromethylpyridinium hydrochloride is obtained. In step S3, the catalyst is one of trifluoroacetic acid, acetic acid, palladium on carbon, acetic anhydride, trifluoropropionic acid, boron trifluoride diethyl ether, boron trifluoride butyl ether, etc. In step S3, 2-amino-1-(3-chloro-5-trifluoromethylpyridin-2-yl)acetone reacts completely with a reducing agent in a solvent within 10-25°C in the presence of a catalyst. The alkaline substance in step S2 is one or two of sodium hydroxide, potassium hydroxide, sodium ethoxide, potassium ethoxide, sodium isopropoxide, and potassium isopropoxide.

2. The method for preparing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride according to claim 1, characterized in that: The hydroxylamine in step S1 is one of hydroxylamine hydrochloride, hydroxylamine sulfate, hydroxylamine aqueous solution, hydroxylamine nitrate, and hydroxylamine phosphate.

3. The method for preparing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride according to claim 2, characterized in that: The hydroxylamine in step S1 is hydroxylamine hydrochloride.

4. The method for preparing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride according to claim 1, characterized in that: In step S1, the first-stage solvent and the second-stage solvent are one or more of alcohols, esters, haloalkanes, ethers, and amides.

5. The method for preparing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride according to claim 4, characterized in that: The solvent in the first stage of step S1 is an alcohol.

6. The method for preparing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride according to claim 4, characterized in that: The solvent in the first stage of step S1 is an aqueous ethanol solution.

7. The method for preparing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride according to claim 4, characterized in that: The solvent in the second stage of step S1 is a haloalkane.

8. The method for preparing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride according to claim 4, characterized in that: The solvent in the second stage of step S1 is dichloromethane.

9. The method for preparing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride according to claim 1, characterized in that: In step S1, the methylamine aqueous solution is a 40% methylamine solution.

10. The method for preparing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride according to claim 1, characterized in that: The molar ratio of raw materials in step S1 is as follows: 2-acetyl-3-chloro-5-trifluoromethylpyridine: hydroxylamine: first-stage alkaline substance: first-stage solvent: p-toluenesulfonyl chloride: second-stage alkaline substance: second-stage solvent = 1:(1-2):(1-2):(20-40):(1-1.5):(1-1.5):(30-50).

11. The method for preparing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride according to claim 10, characterized in that: The molar ratio of raw materials in step S1 is: 2-acetyl-3-chloro-5-trifluoromethylpyridine: hydroxylamine: sodium hydroxide: ethanol and water; p-toluenesulfonyl chloride: methylamine: dichloromethane = 1:1.5:1.6:30:1.2:1.3:

41.

12. The method for preparing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride according to claim 1, characterized in that: In step S2, the solvent is one or two of methanol, ethanol, isopropanol, butanol, dichloromethane, ethyl acetate, and dimethylacetamide.

13. The method for preparing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride according to claim 12, characterized in that: The solvent in step S2 is isopropanol.

14. The method for preparing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride according to claim 12, characterized in that: The alkaline substance in step S2 is potassium isopropoxide.

15. The method for preparing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride according to claim 12, characterized in that: In step S2, the molar ratio of raw materials is: 1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethylamino-p-toluenesulfonate: basic substance: solvent = 1:(1-2):(15-30).

16. The method for preparing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride according to claim 12, characterized in that: In step S2, the molar ratio of raw materials is: 1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethylamino-p-toluenesulfonate: basic substance: solvent = 1:1.5:

20.

17. The method for preparing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride according to claim 1, characterized in that: The solvent in step S3 is one or more of diethyl ether, tetrahydrofuran, dichloromethane, chloroform, dichloroethane, and toluene.

18. The method for preparing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride according to claim 17, characterized in that: The solvent in step S3 is dichloromethane.

19. The method for preparing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride according to claim 1, characterized in that: The reducing agent in step S3 includes one or more of sodium borohydride, lithium aluminum hydride, trimethylchlorosilane, hydrogen, and zinc amalgam.

20. The method for preparing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride according to claim 19, characterized in that: The reducing agent in step S3 is trimethylchlorosilane.

21. The method for preparing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride according to claim 20, characterized in that: In step S3, the catalyst is boron trifluoride diethyl ether.

22. The method for preparing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride according to claim 1, characterized in that: In step S3, the raw material molar ratio is: 2-amino-1-(3-chloro-5-trifluoromethylpyridin-2-yl) ethyl ketone: reducing agent: catalyst: solvent = 1:(1-5):(1-4):(20-40).

23. The method for preparing 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride according to claim 22, characterized in that: In step S3, the raw material molar ratio is: 2-amino-1-(3-chloro-5-trifluoromethylpyridin-2-yl) acetone: trimethylchlorosilane: boron trifluoride ether: solvent = 1:3:2:30.

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