Synthesis method of 2-bromomethyl-5-trifluoromethyl furan

Abstract

The invention discloses a synthesis method of 2-bromomethyl-5-trifluoromethyl furan, which comprises the following steps: S1, carrying out reaction on acetoacetate and halogenated trifluoroacetone under the action of an alkaline substance and a catalyst to generate a 2-acetyl-5, 5, 5-trifluoro-4-oxovalerate crude product; s2, carrying out a cyclization reaction on the 2-acetyl-5, 5, 5-trifluoro-4-oxovalerate crude product, so as to obtain a 2-methyl-5-(trifluoromethyl) furan-3-formate crude product, and carrying out a cyclization reaction on the 2-acetyl-5, 5, 5-trifluoro-4-oxovalerate crude product to obtain a 2-methyl-5-(trifluoromethyl) furan-3-formate crude product; s3, adding an alkaline substance into the crude product, carrying out hydrolysis, and adding acid to adjust the pH value after the hydrolysis is completed, so as to obtain 2-methyl-5-(trifluoromethyl) furan-3-formic acid; s4, the 2-methyl-5-(trifluoromethyl) furan-3-formic acid is subjected to a heating decarboxylation reaction, and 2-methyl-5-(trifluoromethyl) furan is obtained; and S5, carrying out a bromination reaction on the 2-methyl-5-(trifluoromethyl) furan and a bromination reagent to obtain a final product 2-bromomethyl-5-(trifluoromethyl) furan. The raw materials used in the synthesis method are easy to obtain, use of control chemicals is not involved, and industrialization is easy to achieve.

Description

Technical Field

[0001] The invention relates to the technical field of drug preparation, and in particular to a method for synthesizing 2-bromomethyl-5-trifluoromethylfuran. Background Art

[0002] Human gonadotropin-releasing hormone (GnRH) is a key regulator related to sexual development and reproductive function. Since GnRH plays a vital role in the human reproductive system, GnRH and its analogs have been widely used to treat various steroid hormone-dependent diseases, including endometriosis, uterine fibroids and prostate cancer. The structural formula of SK I2496 is as follows. SKI2496 is a new type of human gonadotropin-releasing hormone (GnRH) antagonist with uracil as the structural skeleton developed by SK Chemicals. It can be used to treat hormone-related diseases such as endometriosis, uterine fibroids and prostate cancer. 2-Bromomethyl-5-trifluoromethylfuran is an important intermediate required for the synthesis of SKI2496.

[0003]

[0004] CN115353499A discloses a method for synthesizing 2-bromomethyl-5-trifluoromethylfuran, and its process route is as follows:

[0005]

[0006] The synthesis method uses levulinic acid ester as raw material, reacts levulinic acid ester with ethylene glycol to generate an acetal intermediate, which is then mixed with trifluoromethyltrimethylsilane, and a quaternary ammonium salt is added at low temperature to cause a fluorination reaction, which is heated for hydrolysis, and then reacted with urea and choline chloride for ring closure, followed by bromination to obtain the target compound. This route requires the use of ultra-low temperature (-70°C) reaction, which has high production costs and is not conducive to industrial production. Summary of the invention

[0007] In order to solve the above technical problems, the present invention provides a method for synthesizing 2-bromomethyl-5-trifluoromethylfuran, which reacts under relatively mild conditions and is easy to realize industrialization.

[0008] The present application provides a method for synthesizing 2-bromomethyl-5-trifluoromethylfuran, comprising the following steps:

[0009]

[0010] S1, acetoacetate and halogenated trifluoroacetone react in the presence of an alkaline substance and a catalyst to generate a crude product of 2-acetyl-5,5,5-trifluoro-4-oxopentanoate;

[0011] S2, 2-acetyl-5,5,5-trifluoro-4-oxopentanoate crude product undergoes cyclization reaction to obtain 2-methyl-5-(trifluoromethyl)furan-3-carboxylate crude product;

[0012] S3, adding an alkaline substance to the crude product of 2-methyl-5-(trifluoromethyl)furan-3-carboxylate to cause hydrolysis, and after the hydrolysis is complete, adding acid to adjust the pH value to obtain 2-methyl-5-(trifluoromethyl)furan-3-carboxylic acid;

[0013] S4, 2-methyl-5-(trifluoromethyl)furan-3-carboxylic acid undergoes heating decarboxylation reaction to obtain 2-methyl-5-(trifluoromethyl)furan;

[0014] S5, 2-methyl-5-(trifluoromethyl)furan undergoes bromination reaction with a bromination reagent to obtain the final product 2-bromomethyl-5-trifluoromethylfuran.

[0015] As a preferred embodiment, the acetoacetate in step S1 is selected from any one or more combinations of methyl acetoacetate, ethyl acetoacetate, isopropyl acetoacetate, n-propyl acetoacetate, n-butyl acetoacetate, and tert-butyl acetoacetate.

[0016] As a more preferred embodiment, the acetoacetate in step S1 is methyl acetoacetate or ethyl acetoacetate.

[0017] As a preferred embodiment, the halogenated trifluoroacetone in step S1 is selected from any one or more combinations of chlorotrifluoroacetone, bromotrifluoroacetone and iodotrifluoroacetone.

[0018] As a more preferred embodiment, the halogenated trifluoroacetone in step S1 is chlorotrifluoroacetone.

[0019] The molar equivalent ratio of acetoacetate to halogenated trifluoroacetone is 1:1-1:5, preferably 1:1-1:1.5.

[0020] It should be noted that molar equivalent refers to the stoichiometric relationship between chemical substances in a chemical reaction, and its unit is mole (mol). Equivalent is the amount of chemical substance required or produced in a chemical reaction, which reflects the proportional relationship between the reactions of different chemical substances.

[0021] As a preferred embodiment, the catalyst in step S1 is selected from NaI or KI.

[0022] The molar equivalent ratio of acetoacetate to catalyst is 1:0.01-1:0.5, preferably 1:0.01-1:0.05.

[0023] As a preferred embodiment, the alkaline substance in step S1 is selected from any one or more combinations of sodium hydride, potassium hydride, cesium carbonate, potassium carbonate, sodium methoxide, sodium ethoxide, sodium tert-butoxide, potassium tert-butoxide, methyl lithium, n-butyl lithium, lithium amide, and lithium diisopropylamide.

[0024] As a more preferred embodiment, the alkaline substance in step S1 is selected from sodium hydride and potassium hydride.

[0025] Sodium hydride and potassium hydride are strong alkaline substances, which help the reaction to proceed.

[0026] The molar equivalent ratio of acetoacetate to the alkaline substance is 1:1-1:5, preferably 1:1-1:2.

[0027] The organic solvent used in step S1 is selected from any one or more combinations of n-hexane, tetrahydrofuran, acetonitrile, N,N-dimethylformamide, and ethylene glycol dimethyl ether.

[0028] Preferably, the organic solvent used in step S1 is tetrahydrofuran or ethylene glycol dimethyl ether.

[0029] The reaction temperature of step S1 is -30°C to 120°C, preferably 5°C to 80°C.

[0030] As a preferred embodiment, a protonic acid is further added in step S2, and the protonic acid is selected from any one or more combinations of sulfuric acid, methanesulfonic acid, p-toluenesulfonic acid, formic acid, glacial acetic acid, and hydrochloric acid.

[0031] The molar equivalent ratio of acetoacetate to protic acid is 1:0.1-1:10, preferably 1:1-1:2.

[0032] As a more preferred embodiment, the protonic acid in step S2 is sulfuric acid or methanesulfonic acid.

[0033] The organic solvent used in step S2 is selected from any one or more combinations of acetonitrile, acetic acid, toluene, xylene, NMP, and tetrahydrofuran.

[0034] As a preferred embodiment, the organic solvent used in step S2 is acetonitrile or toluene.

[0035] The reaction temperature in step S2 is 40°C-120°C, preferably 60°C-80°C.

[0036] As a preferred embodiment, the alkaline substance in step S3 is selected from any one or more combinations of lithium hydroxide, sodium hydroxide and potassium hydroxide.

[0037] As a more preferred embodiment, the alkaline substance in step S3 is sodium hydroxide or potassium hydroxide.

[0038] The molar equivalent ratio of acetoacetate to the alkaline substance is 1:1-1:10, preferably 1:1-1:5.

[0039] The organic solvent used in step S3 is selected from any one or more combinations of tetrahydrofuran, acetone, 1,4-dioxane, methanol, ethanol, and isopropanol.

[0040] As a more preferred embodiment, the organic solvent used in step S3 is methanol or ethanol.

[0041] As a preferred embodiment, the acid in step S3 is selected from any one or more combinations of ammonium chloride, citric acid, phosphoric acid, hydrochloric acid, acetic acid, sulfuric acid, and formic acid.

[0042] As a more preferred embodiment, the acid in step S3 is hydrochloric acid or sulfuric acid, and the pH is adjusted to 3.

[0043] As a preferred embodiment, the reaction temperature in step S3 is 40°C-120°C.

[0044] As a more preferred embodiment, the reaction temperature in step S3 is 60°C-80°C.

[0045] As a preferred embodiment, the reaction temperature in step S4 is 100°C-200°C.

[0046] As a more preferred embodiment, the reaction temperature in step S4 is 120°C-160°C.

[0047] The organic solvent used in step S4 is selected from any one or more combinations of DMI, benzyl alcohol, ethylene glycol, ethyl benzoate, NMP, quinoline, and xylene.

[0048] Preferably, the organic solvent used in step S4 is NMP or quinoline.

[0049] In step S4, a metal reagent is also added to play a catalytic role. The metal reagent is selected from any one or more combinations of Cu powder, CuSO4, Cu2SO4, CuSO3, and CuCrO4.

[0050] Preferably, the metal reagent in step S4 is Cu powder or CuSO4.

[0051] The molar equivalent ratio of 2-methyl-5-(trifluoromethyl)furan-3-carboxylic acid to the metal reagent is 1:0.1-1:10, preferably 1:0.1-1:2.

[0052] As a preferred embodiment, the bromination reagent in step S5 is selected from a combination of one or more of tetrabromocyclopentane, bromine, NBS, and dibromohydantoin.

[0053] As a more preferred embodiment, the bromination reagent in step S5 is selected from dibromohydantoin or NBS.

[0054] The molar equivalent ratio of 2-methyl-5-(trifluoromethyl)furan to the brominating agent is 1:1-1:10, preferably 1:1-1:2.

[0055] The organic solvent used in step S5 is selected from any one or more combinations of n-hexane, chloroform, carbon tetrachloride, and 1,2-dichloroethane. Preferably, the organic solvent is chloroform or 1,2-dichloroethane.

[0056] As a preferred embodiment, a catalyst is further added in step S5, and the catalyst is selected from any one of BPO and AIBN or a combination of the two.

[0057] The molar equivalent ratio of 2-methyl-5-(trifluoromethyl)furan to the catalyst is 1:0.01-1:10, preferably 1:0.1-1:1.

[0058] As a preferred embodiment, the reaction temperature in step S5 is 40°C-120°C.

[0059] As a more preferred embodiment, the reaction temperature in step S5 is 60°C-80°C.

[0060] Beneficial effects include:

[0061] 1. The raw materials used in the synthesis method of 2-bromomethyl-5-trifluoromethylfuran of the present invention are easily available, do not involve the use of controlled chemicals, and are easy to realize industrialization.

[0062] 2. The method for synthesizing 2-bromomethyl-5-trifluoromethylfuran of the present invention has relatively mild reaction conditions and does not require reaction at a low temperature of -70°C or a high temperature of more than 200°C. The operation is simple and convenient, and is conducive to industrial production.

[0063] 3. The synthesis method of 2-bromomethyl-5-trifluoromethylfuran of the present invention has stable reaction, simple post-treatment, simplified purification steps and shortened reaction time.

[0064] 4. The synthesis method of 2-bromomethyl-5-trifluoromethylfuran of the present invention has a total yield of up to 56.5% in the entire synthesis route, a stable yield, an easy control of the reaction process, and easy industrial production.

[0065] The concept, specific structure and technical effects of the present invention will be further described below in conjunction with the accompanying drawings to fully understand the purpose, characteristics and effects of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0066] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative labor.

[0067] Figure 1 This is the hydrogen nuclear magnetic spectrum (H-NMR) of 2-bromomethyl-5-trifluoromethylfuran prepared in Example 1 of the present invention.

[0068] Figure 2 It is the gas chromatogram (GC) of 2-bromomethyl-5-trifluoromethylfuran prepared in Example 1 of the present invention. DETAILED DESCRIPTION

[0069] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0070] The compounds or reagents used in the following examples are all commercial compounds or reagents unless otherwise specified.

[0071] Chinese interpretation of the abbreviations of the present invention:

[0072] TLC is thin layer chromatography;

[0073] NaI is sodium iodide;

[0074] EA is ethyl acetate;

[0075] BPO is dibenzoyl peroxide;

[0076] MeOH is methanol;

[0077] NMP is N-methylpyrrolidone;

[0078] NBS is N-bromosuccinimide;

[0079] AIBN is azobisisobutyronitrile;

[0080] DME is ethylene glycol dimethyl ether.

[0081] Embodiment 1:

[0082] The reaction formula of Example 1 is as follows:

[0083]

[0084] Under nitrogen protection, sodium hydride (108.62 g, 1.0 eq) was added to ethylene glycol dimethyl ether (1000 mL), and the temperature in the container was cooled to 5°C by ice bath, and the temperature was controlled between 5-15°C, and then ethyl acetoacetate (353.43 g, 1.0 eq) was added dropwise. After the addition was completed, the temperature in the container was restored to room temperature, and the temperature in the container was heated to 50°C. Chlorotrifluoroacetone (417.72 g, 1.05 eq) was added in a dark environment, and then NaI (4.07 g, 0.01 eq) was added, and then the temperature in the container was raised to 80°C, and the reaction was carried out for 10 hours. TLC detected that the raw material reaction was complete, and the temperature was cooled to room temperature and then filtered, and the mixture was concentrated under reduced pressure to remove most of the solvent and directly put into the next step;

[0085] Under nitrogen protection, acetonitrile (2000 mL) was added to the crude product of the previous step, and then concentrated sulfuric acid (306.07 g, 1.15 eq) with a mass fraction of 98% was added, and the mixture was heated to 80°C for 10 hours. TLC detected that the reaction of the raw material was complete. After cooling to room temperature, H2O (2000 mL) was added to the reaction system, and then extracted with EA (2000 mL × 2). The organic phase was washed with saturated brine, and anhydrous magnesium sulfate was decompressed and dried, and directly used for the next step;

[0086] MeOH (2000 mL) was added to the crude product of the previous step, followed by H2O (2000 mL) and NaOH (325.89 g, 3 eq). After heating to 65°C for 2 hours, TLC detected that the raw material had reacted completely. Methanol was evaporated under reduced pressure, and H2O (1500 mL) was added to the reaction system. After stirring evenly, the pH was adjusted to 3 with hydrochloric acid, filtered, and dried in a 60°C forced air drying oven to obtain a brown solid 2-methyl-5-(trifluoromethyl)furan-3-carboxylic acid (369.0 g, total yield of the first three steps was 70.0%, and purity was 95.7%).

[0087] The first three steps are carried out through continuous reactions, which simplifies the post-experimental treatment, simplifies the purification steps, reduces the loss of intermediates, and shortens the production cycle.

[0088] 2-Methyl-5-(trifluoromethyl)furan-3-carboxylic acid (300 g, 1.0 eq), NMP (800 mL), quinoline (40 mL), Cu powder (29.46 g, 0.3 eq) were added into a 2 L high pressure reactor (purchased from Beijing Sanxi Technology Group Co., Ltd.), heated to 130 ° C, reacted for 15 hours, TLC detected that the raw material reacted completely, and distilled to obtain colorless liquid 2-methyl-5-(trifluoromethyl)furan (211.8 g, yield: 91.3%, purity: 99.21%)

[0089] 2-Methyl-5-(trifluoromethyl)furan (200 g, 1.0 eq), dibromohydantoin (400 g, 1.05 eq), and BPO (32.3 g 0.1 eq) were dissolved in 1,2-dichloroethane (500 mL), and the mixture was heated to 60° C. and reacted for 3 hours. After TLC detection, the reaction of the raw materials was complete. Saturated sodium bisulfite solution was added, and the organic phase was retained after separation. The mixture was subjected to vacuum distillation to obtain a light yellow oily liquid 2-bromomethyl-5-trifluoromethylfuran (269.73 g, yield: 88.4%, purity: 98.96%). Its H-NMR spectrum is as follows: Figure 1 As shown in the gas chromatography (GC) spectrum Figure 2 shown.

[0090] Embodiment 2:

[0091] The reaction formula of Example 2 is as follows:

[0092]

[0093] Under nitrogen protection, potassium tert-butoxide (319.97 g, 1.05 eq) was added to tetrahydrofuran (1000 mL), and the temperature in the container was cooled to 5°C by ice bath, and the temperature was controlled between 5-15°C, and ethyl acetoacetate (353.43 g, 1.0 eq) was added dropwise. After the addition was completed, the temperature in the container was restored to room temperature, and the temperature in the container was heated to 50°C. Chlorotrifluoroacetone (417.72 g, 1.05 eq) was added in a dark environment, and then KI (4.51 g, 0.01 eq) was added. The temperature in the container was then raised to 80°C for reaction for 15 hours. TLC detected that the raw material reaction was complete, and the mixture was cooled to room temperature and filtered, and the mixture was directly added to the next step after reduced pressure distillation.

[0094] Under nitrogen protection, acetonitrile (2000 mL) was added to the crude product of the previous step, and then concentrated sulfuric acid (306.07 g, 1.15 eq) with a mass fraction of 98% was added, and the mixture was heated to 80°C for 10 hours. TLC detected that the raw material had reacted completely. After cooling to room temperature, H2O (2000 mL) was added to the reaction system, and then extracted with EA (2000 mL × 2). The organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, and dried under reduced pressure, and directly used for the next step;

[0095] MeOH (2000 mL) was added to the crude product of the previous step, followed by H2O (2000 mL) and KOH (457.15 g, 3 eq). After heating to 65°C for 2 hours, TLC detected that the raw material had reacted completely. Methanol was evaporated under reduced pressure, and H2O (1500 mL) was added to the reaction system. After stirring evenly, the pH was adjusted to 3 with acetic acid, filtered, and dried in a 60°C forced air drying oven to obtain a brown solid 2-methyl-5-(trifluoromethyl)furan-3-carboxylic acid (335.27 g, total yield of the first three steps was 63.6%, purity: 94.08%).

[0096] Compared with Example 1, since hydrogen is generated after sodium hydride reacts with the substrate and leaves the reaction system, it is more favorable for the reaction. Therefore, when sodium hydride is replaced by potassium tert-butoxide, the total yield of the first three steps is relatively reduced.

[0097] 2-Methyl-5-(trifluoromethyl)furan-3-carboxylic acid (300 g, 1.0 eq) and NMP (800 mL) and Cu powder (29.46 g, 0.3 eq) were added to a 2 L pressure reactor, heated to 150 ° C, and reacted for 12 hours. TLC detected that the raw material reacted completely, and distilled to obtain a colorless liquid 2-methyl-5-(trifluoromethyl)furan (195.8 g, yield: 84.4%, purity: 99.18%)

[0098] Compared with Example 1, the yield decreased significantly from 91.3% to 84.4%, a decrease of 7%, in this step because quinoline was not used.

[0099] 2-Methyl-5-(trifluoromethyl)furan (200 g, 1.0 eq), NBS (249 g, 1.05 eq), AIBN (21.9 g 0.1 eq) were dissolved in 1,2-dichloroethane (500 mL), heated to 60 ° C for 3 hours, TLC detected that the raw materials reacted completely, added saturated sodium bisulfite solution, separated and retained the organic phase, and vacuum distilled to obtain a light yellow oily liquid 2-bromomethyl-5-trifluoromethylfuran (228.2 g, yield: 74.8%, purity: 97.79%)

[0100] Compared with Example 1, in this step, the catalyst was replaced by AIBN, and the bromination reagent was replaced by NBS, and the yield was reduced by 14%.

[0101] Embodiment 3:

[0102] The reaction formula of Example 3 is as follows:

[0103]

[0104] Under nitrogen protection, sodium hydride (108.63 g, 1.0 eq) was added to ethylene glycol dimethyl ether (1000 mL), and the temperature in the container was cooled to 5°C in an ice bath, and the temperature was controlled between 5-10°C, and then ethyl acetoacetate (353.43 g, 1.0 eq) was added dropwise. After the addition was completed, the temperature was restored to room temperature, and the temperature in the container was heated to 50°C. Chlorotrifluoroacetone (417.72 g, 1.05 eq) was added in a dark environment, and then NaI (4.07 g, 0.01 eq) was added. The temperature was then raised to 80°C in the container and reacted for 15 hours. TLC detected that the raw material reacted completely, cooled to room temperature, filtered, and directly added to the next step after reduced pressure distillation;

[0105] Under nitrogen protection, acetonitrile (2000 mL) was added to the crude product of the previous step, and then methanesulfonic acid (300.16 g, 1.15 eq) was added, and the mixture was heated to 80°C for overnight reaction (reaction time was 16 h-18 h). TLC detected that the raw material reaction was complete. After cooling to room temperature, 2000 mL of H2O was added to the reaction system, and then extracted with EA (2000 mL × 2). The organic phase was washed with saturated brine, and anhydrous magnesium sulfate was decompressed and dried, and directly used for the next step;

[0106] EtOH (2000 mL) was added to the crude product of the previous step, followed by H2O (2000 mL) and NaOH (325.89 g, 3 eq). After heating to 65°C for 2 hours, TLC detected that the raw material had reacted completely. The ethanol was dried under reduced pressure, and H2O (1500 mL) was added to the reaction system. After stirring evenly, the pH was adjusted to 3 with sulfuric acid, filtered, and dried in a 60°C forced air drying oven to obtain a brown solid 2-methyl-5-(trifluoromethyl)furan-3-carboxylic acid (362.16 g, total yield of the first three steps was 68.7%, purity: 95.31%).

[0107] 2-Methyl-5-(trifluoromethyl)furan-3-carboxylic acid (300 g, 1.0 eq) and NMP (800 mL) and CuSO4 (74.0 g, 0.3 eq) were added into a 2 L pressure reactor, heated to 150 ° C, and reacted for 12 hours. TLC detected that the raw material reaction was complete, and distillation gave a colorless liquid 2-methyl-5-(trifluoromethyl)furan (190.0 g, yield: 81.9%, purity: 98.74%).

[0108] 2-Methyl-5-(trifluoromethyl)furan (200 g, 1.0 eq), NBS (249 g, 1.05 eq), and AIBN (21.9 g 0.1 eq) were dissolved in chloroform (500 mL), and the mixture was heated to 60° C. and reacted for 3 hours. TLC detected that the reaction of the raw materials was complete, and a saturated sodium bisulfite solution was added. The organic phase was retained after separation, and a light yellow oily liquid (225.8 g, yield: 74.0%, purity: 97.57%) was obtained by vacuum distillation.

[0109] The technical features of the above embodiments may be combined arbitrarily. To make the description concise, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0110] The above-mentioned embodiments only express several implementation methods of the present invention, and the description is relatively specific and detailed, but it cannot be understood as limiting the scope of the patent. It should be pointed out that for ordinary technicians in this field, several modifications and improvements can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention.

Claims

1. A method for synthesizing 2-bromomethyl-5-trifluoromethylfuran, characterized in that: The steps include: S1, acetoacetate and halogenated trifluoroacetone react in the presence of an alkaline substance and a catalyst to generate a crude product of 2-acetyl-5,5,5-trifluoro-4-oxopentanoate; S2, 2-acetyl-5,5,5-trifluoro-4-oxopentanoate crude product undergoes cyclization reaction to obtain 2-methyl-5-(trifluoromethyl)furan-3-carboxylate crude product; S3, adding an alkaline substance to the crude product of 2-methyl-5-(trifluoromethyl)furan-3-carboxylate to cause hydrolysis, and after the hydrolysis is complete, adding acid to adjust the pH value to obtain 2-methyl-5-(trifluoromethyl)furan-3-carboxylic acid; S4, 2-methyl-5-(trifluoromethyl)furan-3-carboxylic acid undergoes heating decarboxylation reaction to obtain 2-methyl-5-(trifluoromethyl)furan; S5, 2-methyl-5-(trifluoromethyl)furan undergoes bromination reaction with a bromination reagent to obtain the final product 2-bromomethyl-5-trifluoromethylfuran.

2. The method for synthesizing 2-bromomethyl-5-trifluoromethylfuran according to claim 1, characterized in that: The acetoacetate in step S1 is selected from any one or more combinations of methyl acetoacetate, ethyl acetoacetate, isopropyl acetoacetate, n-propyl acetoacetate, n-butyl acetoacetate, and tert-butyl acetoacetate.

3. The method for synthesizing 2-bromomethyl-5-trifluoromethylfuran according to claim 1, characterized in that: The halogenated trifluoroacetone in step S1 is selected from any one or more combinations of chlorotrifluoroacetone, bromotrifluoroacetone and iodotrifluoroacetone.

4. The method for synthesizing 2-bromomethyl-5-trifluoromethylfuran according to claim 1, characterized in that: The alkaline substance in step S1 is selected from any one or more combinations of sodium hydride, potassium hydride, cesium carbonate, potassium carbonate, sodium methoxide, sodium ethoxide, sodium tert-butoxide, potassium tert-butoxide, methyl lithium, n-butyl lithium, lithium amide, and lithium diisopropylamide.

5. The method for synthesizing 2-bromomethyl-5-trifluoromethylfuran according to claim 1, characterized in that: The catalyst in step S1 is selected from NaI or KI.

6. The method for synthesizing 2-bromomethyl-5-trifluoromethylfuran according to claim 1, characterized in that: In step S2, a protonic acid is also added, and the protonic acid is selected from any one or more combinations of sulfuric acid, methanesulfonic acid, p-toluenesulfonic acid, formic acid, glacial acetic acid, and hydrochloric acid.

7. The method for synthesizing 2-bromomethyl-5-trifluoromethylfuran according to claim 1, characterized in that: The alkaline substance in step S3 is selected from any one or more combinations of lithium hydroxide, sodium hydroxide and potassium hydroxide.

8. The method for synthesizing 2-bromomethyl-5-trifluoromethylfuran according to claim 1, characterized in that: The reaction temperature in step S4 is 100°C-200°C.

9. The method for synthesizing 2-bromomethyl-5-trifluoromethylfuran according to claim 1, characterized in that: The brominating agent in step S5 is selected from a combination of one or more of tetrabromocyclic ketone, bromine, NBS, and dibromohydantoin.

10. The method for synthesizing 2-bromomethyl-5-trifluoromethylfuran according to claim 1, characterized in that: In step S5, a catalyst is also added, and the catalyst is selected from any one of BPO and AIBN or a combination of the two.

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