Synthesis method of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine
Through the combination of catalytic dechlorination, Vilsmeier-Haack reaction and Henry reaction, the synthesis efficiency of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine was successfully improved, and the long route and recovery in the existing technology were solved. The problems of low rate and large resource waste have achieved an efficient and simple preparation process.
Patent Information
- Application Number
- CN202411341472.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-25
- Publication Date
- 2024-12-31
AI Technical Summary
The existing synthesis method of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine has problems such as long routes, low yields, large waste of resources, complicated post-treatment processes, and low preparation efficiency and low selectivity.
2,3-dichloro-5-trifluoromethylpyridine was catalyzed and then formoylated with Vilsmeier reagent, followed by Henry reaction with nitromethane, and finally 3-chloro-2-ammonia was obtained by hydrogenation reduction. Ethyl-5-trifluoromethylpyridine. The method includes catalytic dechlorination in step S1, Vilsmeier-Haack reaction in step S2, addition reaction in step S3, and hydrogenation reduction in step S4, and reaction with hydrogen gas using a catalyst such as palladium/carbon, platinum/carbon, and hydrogen gas.
Improve the synthesis efficiency of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine, simplify the post-treatment process, reduce safety risks, realize efficient and simple preparation, reduce contaminant treatment, product purity and The yield is significantly improved.
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Abstract
Description
Technical Field
[0001] The invention relates to the field of organic synthesis, and in particular to a method for synthesizing 3-chloro-2-aminoethyl-5-trifluoromethylpyridine. Background Art
[0002] Fluopyram is a benzamide fungicide containing a pyridine structure developed by Bayer. Fluopyram has a broad fungicide spectrum and can be applied to a variety of diseases of more than 70 crops, such as vegetables, pears and stone fruits, grapes and field crops. It can treat a variety of diseases caused by Sclerotinia, Mycelium, powdery mildew and Botrytis cinerea. It is a fungicide with low toxicity, high efficacy, strong systemicity and environmental friendliness. Due to the advantages of safety, low dosage and long lasting effect, fluopyram has great development potential in the pesticide market in the future.
[0003] 3-Chloro-2-aminoethyl-5-trifluoromethylpyridine is an important intermediate for the synthesis of fluopyram. At present, domestic manufacturers have not reported a more mature fluopyram preparation technology. There are two main synthetic routes for 3-chloro-2-aminoethyl-5-trifluoromethylpyridine reported in the literature. For example, E Fodor et al. studied a method of obtaining the target product by condensing 2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl] diethyl malonate with 2-(chloromethyl)isoindoline-1,3-dione, decarboxylating, and hydrazinolysis. The raw material 2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl] diethyl malonate is prepared from 2,3-dichloro-5-trifluoromethylpyridine and diethyl malonate. This method of synthesizing primary amines through Gabriel has the main disadvantages of long route and low yield (RevueRoumaine De Chimie, 2010, 55(9): 559-564).
[0004] Another method is to obtain the intermediate 2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]acetonitrile by substitution and hydrolysis with methyl cyanoacetate or ethyl cyanoacetate, and finally obtain 3-chloro-2-aminoethyl-5-trifluoromethylpyridine by palladium-carbon catalytic hydrogenation (WO 2015071230, EP 1674455). Since 2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]acetonitrile is easy to generate secondary amines or tertiary amines as byproducts during the hydrogenation reduction process, the chlorine on the pyridine ring is also easy to be hydrogenolyzed, resulting in low selectivity of the reduction reaction.
[0005] With the increasing market demand and the increasing requirements for environmental protection, the above-mentioned existing preparation methods of 2,3-dichloro-5-trifluoromethylpyridine have the disadvantages of low preparation efficiency, large waste of resources, and complicated post-processing procedures. Summary of the invention
[0006] In view of the defects in the prior art, the object of the present invention is to provide a method for synthesizing 3-chloro-2-aminoethyl-5-trifluoromethylpyridine.
[0007] A method for synthesizing 3-chloro-2-aminoethyl-5-trifluoromethylpyridine provided by the present invention comprises the following steps:
[0008] S1, using 2,3-dichloro-5-trifluoromethylpyridine as a raw material, and obtaining 3-chloro-5-trifluoromethylpyridine by catalytic dechlorination;
[0009] S2, the product obtained in step S1 is subjected to Vilsmeier-Haack reaction with Vilsmeier reagent to obtain 3-chloro-5-trifluoromethylpyridine-2-carboxaldehyde;
[0010] S3, the product obtained in step S2 is subjected to Henry reaction with nitromethane to obtain 3-chloro-2-(2-nitrovinyl)-5-trifluoromethylpyridine;
[0011] S4. The product obtained in step S3 is subjected to hydrogenation reduction to obtain 3-chloro-2-aminoethyl-5-trifluoromethylpyridine.
[0012] The catalyst for the catalytic reduction reaction in step S1 is selected from palladium / carbon, platinum / carbon, platinum dioxide, Raney nickel, Raney cobalt, and ruthenium trichloride, and the reducing agent is selected from hydrogen.
[0013] The amount of catalyst added in step S1 is 0.05-2% of the mass of 2,3-dichloro-5-trifluoromethylpyridine, the reaction pressure is 0.2-3MPa, and the reaction can be carried out at a temperature of 100-360°C, preferably 120-300°C.
[0014] The catalytic reduction reaction in step S1 is carried out in a solvent, and the solvent is one or a mixture of two of water, C1-C4 aliphatic alcohol, tetrahydrofuran, 2-methyltetrahydrofuran, ethyl acetate, and butyl acetate.
[0015] The Vilsmeier reagent in step S2 can be prepared by N,N-disubstituted amide and acyl chloride compounds, wherein the N,N-disubstituted amide is preferably N,N-dimethylformamide, and the acyl chloride compound is selected from phosphorus oxychloride, thionyl chloride, oxalyl chloride, phosgene, solid phosgene, preferably phosgene; the molar ratio of 3-chloro-5-trifluoromethylpyridine to the Vilsmeier reagent is 1:1-3, preferably 1:1.2.
[0016] The Vilsmeier-Haack reaction in step S2 is carried out in a solvent, and the solvent is one of dichloromethane, dichloroethane, chlorobenzene, dichlorobenzene, N,N-dimethylformamide, and N,N-dimethylacetamide.
[0017] In step S3, the molar ratio of 3-chloro-5-trifluoromethylpyridine-2-carbaldehyde to nitromethane is 1:1-1.5, preferably 1:1.1-1.2.
[0018] The Henry reaction in step S3 is carried out in a solvent, and the solvent is one of water, C1-C4 aliphatic alcohol, dichloromethane, dichloroethane, chlorobenzene, dichlorobenzene, tetrahydrofuran, 2-methyltetrahydrofuran, and acetonitrile.
[0019] The catalyst for the hydrogenation reduction reaction in step S4 is selected from palladium / carbon, platinum / carbon, platinum dioxide, Raney nickel, Raney cobalt, and ruthenium trichloride, and the reducing agent is selected from hydrogen.
[0020] The amount of catalyst added in step S4 is 0.01-2% of the mass of 3-chloro-2-(2-nitrovinyl)-5-trifluoromethylpyridine, the reaction pressure is 0.2-5MPa, and the reaction can be carried out at a temperature of 60-250°C, preferably 100-200°C.
[0021] Compared with the prior art, the present invention has the following beneficial effects:
[0022] (1) In the synthesis method of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine of the present invention, the boiling point of the starting material 2,3-dichloro-5-trifluoromethylpyridine is 80° C. (20 mmHg), the dechlorination efficiency of step S1 is high, and a fixed bed reactor can be used for the dechlorination, which is easy to realize continuous operation. The product 3-dichloro-5-trifluoromethylpyridine does not need post-treatment and is directly put into the next step of reaction, which reduces the treatment of pollutants.
[0023] (2) In the method for synthesizing 3-chloro-2-aminoethyl-5-trifluoromethylpyridine of the present invention, step S2 adopts the classical Vilsmeier-Haack formylation reaction, and the reaction conditions are mild, thereby achieving efficient synthesis of 3-chloro-5-trifluoromethylpyridine-2-carboxaldehyde.
[0024] (3) In the method for synthesizing 3-chloro-2-aminoethyl-5-trifluoromethylpyridine of the present invention, step S3 adopts Henry reaction, which is a rapid reaction with high conversion rate, few side reactions and simple post-treatment process.
[0025] (4) The method for synthesizing 3-chloro-2-aminoethyl-5-trifluoromethylpyridine of the present invention, step S4 can simultaneously reduce the olefin bond and the nitro group under catalytic conditions, has the advantages of high efficiency, simplicity, mild reaction conditions, etc., can effectively improve the preparation efficiency and reduce safety risks. DETAILED DESCRIPTION
[0026] The present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.
[0027] The invention discloses a method for synthesizing 3-chloro-2-aminoethyl-5-trifluoromethylpyridine. 2,3-dichloro-5-trifluoromethylpyridine is used as a raw material, and 3-chloro-2-aminoethyl-5-trifluoromethylpyridine is prepared through dechlorination, formylation, addition and reduction reactions.
[0028] Specifically, the following steps are included:
[0029] S1, using 2,3-dichloro-5-trifluoromethylpyridine as a raw material, and obtaining 3-chloro-5-trifluoromethylpyridine by catalytic dechlorination;
[0030] S2, the product obtained in step S1 is subjected to Vilsmeier-Haack reaction with Vilsmeier reagent to obtain 3-chloro-5-trifluoromethylpyridine-2-carboxaldehyde;
[0031] S3, the product obtained in step S2 is subjected to Henry reaction with nitromethane to obtain 3-chloro-2-(2-nitrovinyl)-5-trifluoromethylpyridine;
[0032] S4. The product obtained in step S3 is subjected to hydrogenation reduction to obtain 3-chloro-2-aminoethyl-5-trifluoromethylpyridine.
[0033] Specifically, the reaction formula of this embodiment is:
[0034]
[0035] The preparation method of this embodiment has the advantages of high efficiency, simplicity, mild reaction conditions, and easy industrialization. It can effectively shorten the reaction time, improve production efficiency, and reduce safety risks.
[0036] Example 1
[0037] Step (1) Synthesis of 3-chloro-5-trifluoromethylpyridine:
[0038]
[0039] 2,3-Dichloro-5-trifluoromethylpyridine (21.6 g, 0.1 mol), water-methanol (v / v=1:1, 220 mL), and 5% Pd / C (1 g) were added to a 1L high-pressure reactor in sequence. The system was replaced with nitrogen 3 times and hydrogen 2 times in sequence, and then hydrogen was added until the pressure was stabilized at 0.7 MPa. The hydrogen valve was closed, and the temperature was slowly raised to 100°C for insulation reaction. Sampling and tracking were performed. After the reaction was completed, the pressure was restored to normal pressure, and the catalyst was removed by hot filtration. The pH was adjusted to neutral with 5% sodium carbonate solution, the organic layer was separated, and 3-chloro-5-trifluoromethylpyridine was obtained by decompression and desolventization. The product purity was 98.2% and the yield was 93.6% according to liquid phase external standard method analysis.
[0040] Step (2) 3-chloro-5-trifluoromethylpyridine-2-carbaldehyde:
[0041]
[0042] N, N-dimethylformamide (48.2 g, 0.66 mol) and 350 mL of dichloromethane were added to a 1 L stirred reactor in sequence. After the measured amount of phosgene was introduced, white Vilsmeier salt was generated, and then an appropriate amount of nitrogen was introduced to remove the residual phosgene. Subsequently, 3-chloro-5-trifluoromethylpyridine (108.9 g, 0.6 mol) was added to the system, and the temperature was slowly raised to 60°C. After the reaction was kept at this temperature for 5 hours, the temperature was lowered to room temperature, 50 ml of 1% sodium bicarbonate solution was added dropwise, and stirring was continued for 0.5 hours. The organic layer was separated, and the solvent was removed under reduced pressure to obtain 3-chloro-5-trifluoromethylpyridine-2-carboxaldehyde. The product purity was 97.6% and the yield was 90.3% according to the liquid phase external standard method.
[0043] Step (3) 3-chloro-2-(2-nitrovinyl)-5-trifluoromethylpyridine:
[0044]
[0045] 3-Chloro-5-trifluoromethylpyridine-2-carboxaldehyde (41.9 g, 0.2 mol) and 200 mL of methanol were added to a 1 L stirred reactor in sequence. After the system was cooled to 0°C, (14.6 g, 0.24 mol) of nitromethane was added, and 70 mL of 12% sodium hydroxide solution was slowly added dropwise. After the addition was completed, the mixture was kept warm for 1 h. Then, 2 mol / L dilute hydrochloric acid was continued to be added dropwise at 0°C to adjust the pH to neutral. The mixture was filtered, and the filter cake was washed and dried to obtain 3-chloro-2-(2-nitrovinyl)-5-trifluoromethylpyridine. According to liquid phase external standard method analysis, the product had a purity of 95.1% and a yield of 88.6%.
[0046] Step (4) 3-chloro-2-aminoethyl-5-trifluoromethylpyridine:
[0047]
[0048] 3-Chloro-2-(2-nitrovinyl)-5-trifluoromethylpyridine (50.5 g, 0.2 mol), Raney cobalt (wet weight 10 g), and 300 mL of ethanol were added to a 1 L high pressure reactor in sequence. The system was replaced with nitrogen 3 times and hydrogen 2 times in sequence, and then hydrogen was added until the pressure was stabilized at 1 MPa. The hydrogen valve was closed, and the temperature was slowly raised to 75° C., and the reaction was kept warm. Sampling and tracking were performed. After the reaction was completed, the pressure was restored to normal pressure, filtered, and the filtrate was distilled under reduced pressure. The residue was crystallized with 150 mL of isopropyl ether, filtered, and dried to obtain 3-chloro-2-aminoethyl-5-trifluoromethylpyridine. According to liquid phase external standard method analysis, the product purity was 93.6% and the yield was 89.2%.
[0049] Example 2
[0050] The synthesis steps are the same as in Example 1, except that:
[0051] In step (1), the catalyst is ruthenium trichloride (0.9 g), the solvent is tetrahydrofuran (250 mL), the hydrogen pressure is 0.9 MPa, the reaction temperature is 150° C., the purity of 3-chloro-5-trifluoromethylpyridine is 97.7%, and the yield is 93.7%.
[0052] In step (2), the solvent is dichloroethane, the molar ratio of 3-chloro-5-trifluoromethylpyridine to Vilsmeier reagent is 1:1, the purity of 3-chloro-5-trifluoromethylpyridine-2-carboxaldehyde is 91.9%, and the yield is 92.6%.
[0053] In step (3), the solvent is ethanol, the molar ratio of 3-chloro-5-trifluoromethylpyridine-2-carboxaldehyde to nitromethane is 1:1, the purity of 3-chloro-2-(2-nitrovinyl)-5-trifluoromethylpyridine is 88.3%, and the yield is 88.2%.
[0054] In step (4), the catalyst used was 5% Pt / C (1.1 g), the hydrogen pressure was 0.2 MPa, the reaction temperature was 90° C., the purity of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine was 96.4%, and the yield was 96.1%.
[0055] Example 3
[0056] The synthesis steps are the same as in Example 1, except that:
[0057] In step (1), the catalyst is Raney cobalt (wet weight 6 g), the solvent is ethyl acetate (300 mL), the hydrogen pressure is 2.8 MPa, the reaction temperature is 100° C., the purity of 3-chloro-5-trifluoromethylpyridine is 98.4%, and the yield is 88.9%.
[0058] In step (2), the solvent is N,N-dimethylformamide, the molar ratio of 3-chloro-5-trifluoromethylpyridine to Vilsmeier reagent is 1:15, the purity of 3-chloro-5-trifluoromethylpyridine-2-carboxaldehyde is 96.9%, and the yield is 94.6%.
[0059] In step (3), the solvent is dichloromethane, the molar ratio of 3-chloro-5-trifluoromethylpyridine-2-carboxaldehyde to nitromethane is 1:1.4, the purity of 3-chloro-2-(2-nitrovinyl)-5-trifluoromethylpyridine is 91.8%, and the yield is 92.2%.
[0060] In step (4), the catalyst is Raney nickel (wet weight 10 g), the hydrogen pressure is 4.5 MPa, the reaction temperature is 250° C., the purity of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine is 89.9%, and the yield is 85.8%.
[0061] Example 4
[0062] The synthesis steps are the same as in Example 1, except that:
[0063] Step (1) The catalyst is Raney nickel (wet weight 15 g), the solvent is water-isopropanol (v / v=1:1.5, 300 mL), the hydrogen pressure is 2.2 MPa, the reaction temperature is 110° C., the purity of 3-chloro-5-trifluoromethylpyridine is 89.5%, and the yield is 90.7%.
[0064] In step (2), the solvent is N,N-dimethylacetamide, the molar ratio of 3-chloro-5-trifluoromethylpyridine to Vilsmeier reagent is 1:2, the purity of 3-chloro-5-trifluoromethylpyridine-2-carboxaldehyde is 95.0%, and the yield is 94.4%.
[0065] In step (3), the solvent is dichloroethane, the molar ratio of 3-chloro-5-trifluoromethylpyridine-2-carboxaldehyde to nitromethane is 1:1.5, the purity of 3-chloro-2-(2-nitrovinyl)-5-trifluoromethylpyridine is 88.7%, and the yield is 93.1%.
[0066] In step (4), the catalyst used was 5% Pd / C (2 g), the hydrogen pressure was 5 MPa, the reaction temperature was 120° C., the purity of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine was 92.9%, and the yield was 91.0%.
[0067] Example 5
[0068] The synthesis steps are the same as in Example 1, except that:
[0069] Step (1) The catalyst was 2% Pt / C (2.5 g), the solvent was water-tetrahydrofuran (v / v=1:2, 250 mL), the hydrogen pressure was 1.6 MPa, the reaction temperature was 220° C., the purity of 3-chloro-5-trifluoromethylpyridine was 90.5%, and the yield was 89.2%.
[0070] In step (2), the solvent is N,N-dimethylacetamide, the molar ratio of 3-chloro-5-trifluoromethylpyridine to Vilsmeier reagent is 1:3, the purity of 3-chloro-5-trifluoromethylpyridine-2-carboxaldehyde is 90.4%, and the yield is 95.1%.
[0071] In step (3), tetrahydrofuran is used as the solvent, the molar ratio of 3-chloro-5-trifluoromethylpyridine-2-carboxaldehyde to nitromethane is 1:1.4, the purity of 3-chloro-2-(2-nitrovinyl)-5-trifluoromethylpyridine is 90.2%, and the yield is 85.9%.
[0072] In step (4), the catalyst is ruthenium trichloride (1.8 g), the hydrogen pressure is 1.6 MPa, the reaction temperature is 100° C., the purity of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine is 93.6%, and the yield is 95.4%.
[0073] Example 6
[0074] The synthesis steps are the same as in Example 1, except that:
[0075] In step (1), platinum dioxide (1 g) was used as the catalyst, ethanol (280 mL) was used as the solvent, the hydrogen pressure was 1.2 MPa, the reaction temperature was 140° C., the purity of 3-chloro-5-trifluoromethylpyridine was 87.6%, and the yield was 94.2%.
[0076] In step (2), the solvent is dichloroethane, the molar ratio of 3-chloro-5-trifluoromethylpyridine to Vilsmeier reagent is 1:2.2, the purity of 3-chloro-5-trifluoromethylpyridine-2-carboxaldehyde is 98.1%, and the yield is 92.8%.
[0077] In step (3), the solvent is acetonitrile, the molar ratio of 3-chloro-5-trifluoromethylpyridine-2-carboxaldehyde to nitromethane is 1:1.2, the purity of 3-chloro-2-(2-nitrovinyl)-5-trifluoromethylpyridine is 86.6%, and the yield is 89.0%.
[0078] In step (4), the catalyst used was 5% Pd / C (3.5 g), the hydrogen pressure was 2.2 MPa, the reaction temperature was 210° C., the purity of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine was 92.9%, and the yield was 91.0%.
[0079] Example 7
[0080] The synthesis steps are the same as in Example 1, except that:
[0081] In step (1), the catalyst is selected from Raney cobalt (wet weight 12.5 g), the solvent is selected from butyl acetate (250 mL), the hydrogen pressure is 2 MPa, the reaction temperature is 180° C., the purity of 3-chloro-5-trifluoromethylpyridine is 90.0%, and the yield is 95.2%.
[0082] In step (2), the solvent is chlorobenzene, the molar ratio of 3-chloro-5-trifluoromethylpyridine to Vilsmeier reagent is 1:2.5, the purity of 3-chloro-5-trifluoromethylpyridine-2-carboxaldehyde is 91.2%, and the yield is 89.7%.
[0083] In step (3), the solvent is 2-methyltetrahydrofuran, the molar ratio of 3-chloro-5-trifluoromethylpyridine-2-carboxaldehyde to nitromethane is 1:1.15, the purity of 3-chloro-2-(2-nitrovinyl)-5-trifluoromethylpyridine is 97.2%, and the yield is 95.5%.
[0084] In step (4), platinum dioxide (2.6 g) was used as the catalyst, the hydrogen pressure was 3 MPa, the reaction temperature was 180° C., the purity of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine was 90.5%, and the yield was 86.8%.
[0085] Example 8
[0086] The synthesis steps are the same as in Example 1, except that:
[0087] Step (1) The catalyst is 10% Pd / C (3 g), the solvent is water-ethanol (v / v=1:3, 250 mL), the hydrogen pressure is 2.5 MPa, the reaction temperature is 250° C., the purity of 3-chloro-5-trifluoromethylpyridine is 91.6%, and the yield is 87.6%.
[0088] In step (2), the solvent is o-dichlorobenzene, the molar ratio of 3-chloro-5-trifluoromethylpyridine to Vilsmeier reagent is 1:1.8, the purity of 3-chloro-5-trifluoromethylpyridine-2-carboxaldehyde is 89.6%, and the yield is 94.3%.
[0089] In step (3), the solvent is n-butanol, the molar ratio of 3-chloro-5-trifluoromethylpyridine-2-carboxaldehyde to nitromethane is 1:1.12, the purity of 3-chloro-2-(2-nitrovinyl)-5-trifluoromethylpyridine is 97.2%, and the yield is 94.3%.
[0090] In step (4), the catalyst used was 10% Pd / C (3.2 g), the hydrogen pressure was 0.4 MPa, the reaction temperature was 160° C., the purity of 3-chloro-2-aminoethyl-5-trifluoromethylpyridine was 91.5%, and the yield was 85.7%.
[0091] The above description is only the preferred embodiment of the present application and is not intended to limit the present application. For those skilled in the art, the present application may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.
Claims
1. A method for synthesizing 3-chloro-2-aminoethyl-5-trifluoromethylpyridine, characterized in that: The following steps are involved: S1. Using 2,3-dichloro-5-trifluoromethylpyridine as a raw material, 3-chloro-5-trifluoromethylpyridine is obtained by catalytic dechlorination; S2. The product obtained in step S1 is subjected to Vilsmeier-Haack reaction with Vilsmeier reagent to obtain 3-chloro-5-trifluoromethylpyridine-2-carboxaldehyde; S3. The product obtained in step S2 is subjected to Henry reaction with nitromethane to obtain 3-chloro-2-(2-nitrovinyl)-5-trifluoromethylpyridine; S4. The product obtained in step S3 is subjected to hydrogenation reduction to obtain 3-chloro-2-aminoethyl-5-trifluoromethylpyridine.
2. The method for synthesizing 3-chloro-2-aminoethyl-5-trifluoromethylpyridine according to claim 1, characterized in that: The catalyst for the catalytic reduction reaction in step S1 is selected from palladium / carbon, platinum / carbon, platinum dioxide, Raney nickel, Raney cobalt, and ruthenium trichloride; and the reducing agent is selected from hydrogen.
3. The method for synthesizing 3-chloro-2-aminoethyl-5-trifluoromethylpyridine according to claim 1, characterized in that: The amount of catalyst added in step S1 is 0.05-2% of the mass of 2,3-dichloro-5-trifluoromethylpyridine, the reaction pressure is 0.2-3 MPa, and the reaction is carried out at a temperature of 100-360°C.
4. The method for synthesizing 3-chloro-2-aminoethyl-5-trifluoromethylpyridine according to claim 1, characterized in that: The catalytic reduction reaction in step S1 is carried out in a solvent, and the solvent is one or a mixture of two of water, C1-C4 aliphatic alcohol, tetrahydrofuran, 2-methyltetrahydrofuran, ethyl acetate, and butyl acetate.
5. The method for synthesizing 3-chloro-2-aminoethyl-5-trifluoromethylpyridine according to claim 1, characterized in that: The Vilsmeier reagent in step S2 can be prepared by N,N-disubstituted amide and acyl chloride compounds, wherein the N,N-disubstituted amide is preferably N,N-dimethylformamide, and the acyl chloride compound is selected from phosphorus oxychloride, thionyl chloride, oxalyl chloride, phosgene, and solid phosgene; the molar ratio of 3-chloro-5-trifluoromethylpyridine to the Vilsmeier reagent is 1:1-3.
6. The method for synthesizing 3-chloro-2-aminoethyl-5-trifluoromethylpyridine according to claim 1, characterized in that: The Vilsmeier-Haack reaction in step S2 is carried out in a solvent, and the solvent is one of dichloromethane, dichloroethane, chlorobenzene, dichlorobenzene, N,N-dimethylformamide, and N,N-dimethylacetamide.
7. The method for synthesizing 3-chloro-2-aminoethyl-5-trifluoromethylpyridine according to claim 1, characterized in that: In step S3, the molar ratio of 3-chloro-5-trifluoromethylpyridine-2-carbaldehyde to nitromethane is 1:1-1.
5.
8. The method for synthesizing 3-chloro-2-aminoethyl-5-trifluoromethylpyridine according to claim 1, characterized in that: The Henry reaction in step S3 is carried out in a solvent, and the solvent is one of water, C1-C4 aliphatic alcohol, dichloromethane, dichloroethane, chlorobenzene, dichlorobenzene, tetrahydrofuran, 2-methyltetrahydrofuran, and acetonitrile.
9. The method for synthesizing 3-chloro-2-aminoethyl-5-trifluoromethylpyridine according to claim 1, characterized in that: The catalyst for the hydrogenation reduction reaction in step S4 is selected from palladium / carbon, platinum / carbon, platinum dioxide, Raney nickel, Raney cobalt, and ruthenium trichloride, and the reducing agent is selected from hydrogen.
10. The method for synthesizing 3-chloro-2-aminoethyl-5-trifluoromethylpyridine according to claim 1, characterized in that: The amount of catalyst added in step S4 is 0.01-2% of the mass of 3-chloro-2-(2-nitrovinyl)-5-trifluoromethylpyridine, the reaction pressure is 0.2-5MPa, and the reaction can be carried out at a temperature of 60-250°C.