2-[2-(2, 2, 2-trifluoroethoxy) phenoxy] ethyl methanesulfonate and preparation method thereof

Abstract

The invention provides 2-[2-(2, 2, 2-trifluoroethoxy) phenoxy] ethyl methanesulfonate and a preparation method thereof, and relates to the technical field of medicine synthesis. The preparation method comprises the following steps: sequentially carrying out etherification, Ullmann coupling and sulfonylation reaction on o-halogen phenol serving as a raw material to obtain 2-[2-(2, 2, 2-trifluoroethoxy) phenoxy] ethyl methanesulfonate; the synthetic route is novel, reaction steps are few, raw materials and reagents used in the reaction are cheap and easy to obtain, an expensive palladium catalyst and a dangerous reagent do not need to be used, and the method is environmentally friendly, uniform-temperature and controllable in reaction condition, simple and convenient to operate, high in product purity, high in yield and suitable for industrial production.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical synthesis, and in particular to 2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate and a preparation method thereof. Background Art

[0002] Silodosin, chemically known as 2,3-dihydro-1-(3-hydroxypropyl)-5-[(2R)-2-[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethylamino]propyl]-1H-indole-7-carboxamide, is an a1A receptor antagonist developed by Kissei Pharmaceuticals of Japan. It was first launched in Japan in May 2006 and officially launched in the United States in October 2008 with FDA approval under the trade name Urief. Silodosin is clinically used to treat symptoms associated with benign prostatic hyperplasia (BPH) or hypertrophy. Among them, 2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate is a key intermediate in the synthesis of silodosin.

[0003] At present, there are several main routes for the synthesis of 2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate.

[0004] Route 1: Chinese Chemical Letters. 200819(1): 59-60, reported a synthetic route for [2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate (1), which uses o-nitrochlorobenzene as the starting material, and undergoes trifluoroethanol etherification, palladium-carbon nitro reduction, diazotization and hydrolysis to obtain o-hydroxytrifluoroethyl ether, which can be further used to prepare silodosin key intermediate 2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate.

[0005]

[0006] This route uses expensive palladium metal catalysis and requires diazotization, which is relatively dangerous and not conducive to industrialization.

[0007] Route 2: European Patent EP600675 reported a synthetic route for [2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate, which uses o-methoxyphenol (guaiacol) as the starting material, is etherified with trifluoroiodoethane, demethylated with boron tribromide, etherified with ethyl bromoacetate, reduced with lithium aluminum tetrahydride, and finally sulfonylated with methanesulfonyl chloride to obtain [2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate.

[0008]

[0009] This route requires the use of expensive and difficult-to-store trifluoroiodoethane, and requires the use of expensive LAH as a reducing agent. The conditions are harsh and not suitable for industrialization.

[0010] Route 3: Using catechol as the raw material, trifluoroethyl ether is prepared and then reacted with ethylene dimethylsulfonate to obtain the final product.

[0011]

[0012] The first step of this route to make trifluoroethyl ether has selectivity problems and is difficult to purify, which greatly affects the atomic utilization rate and is not suitable for industrial production.

[0013] Route 4: Patent CN109516933B in 2018 reported that salicylaldehyde was used as raw material, and [2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate was obtained through condensation with ethylene carbonate, Dakin oxidation, etherification, and sulfonylation.

[0014]

[0015] This route uses explosive peroxides for oxidation and also has problems with etherification selectivity and purification, which is not conducive to industrialization. Summary of the invention

[0016] 1. Technical issues to be resolved

[0017] In view of the deficiencies in the prior art, the present invention provides a 2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate and a preparation method thereof, which solves the technical problem of low yield and purity of the existing preparation method of 2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate.

[0018] (II) Technical solution

[0019] To achieve the above objectives, the present invention is implemented through the following technical solutions:

[0020] In one aspect, the present invention provides a method for preparing 2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate, the preparation method comprising taking o-halogenphenol as a raw material, sequentially subjecting etherification, Ullmann coupling, and sulfonylation reactions to obtain 2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate;

[0021] The synthetic route is:

[0022]

[0023] The preparation method comprises the following steps:

[0024] S1, dissolving the compound of formula 1 in a solvent, adding an etherifying agent and a base, stirring and reacting at a temperature of T1, adding water to quench the reaction after the reaction is completed, extracting with an extractant, drying and concentrating to obtain a compound of formula 2;

[0025] S2, dissolving the compound of formula 2 in a solvent, adding a base and a copper salt, heating to T2 for reaction, and after the reaction is completed, pouring water to quench, extracting with an extractant, filtering and drying to obtain a compound of formula 3;

[0026] S3, dissolving the compound of formula 3 in a solvent, adding a base, dropping a sulfonylating agent, stirring and reacting at temperature T3, after the reaction is complete, cooling to room temperature, dropping an acid to quench, extracting with an extraction solvent, washing, drying, concentrating, and crystallizing with a crystallization solvent to obtain a compound of formula 4, i.e., 2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate.

[0027] Preferably, in S1, the solvent is selected from at least one of N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), and N-methylpyrrolidone (NMP), preferably N,N-dimethylformamide (DMF);

[0028] Preferably, S1 satisfies at least one of the following conditions:

[0029] The mass volume ratio of the compound of formula 1 to the solvent is 1 g: (2-10) ml, preferably 1 g: (6-8) ml;

[0030] The molar ratio of the compound of formula 1, the etherification agent and the base is 1:(1-3):(2-5), preferably 1:(1-1.5):(2-3).

[0031] Preferably, S1 satisfies at least one of the following conditions:

[0032] The etherification agent is selected from one or more of trifluoroethanol, trifluoroethyl methanesulfonate, and trifluoroethyl p-toluenesulfonate, preferably trifluoroethyl p-toluenesulfonate;

[0033] The base is selected from one or more of sodium bicarbonate, potassium bicarbonate, potassium carbonate, sodium carbonate, pyridine, and triethylamine, preferably potassium carbonate.

[0034] Preferably, the T1 temperature is 80-180°C, preferably 100-140°C.

[0035] Preferably, S2 satisfies at least one of the following conditions:

[0036] The mass volume ratio of the compound of formula 2 and the solvent is 1g:(2-10)ml, preferably 1g:(6-8)ml;

[0037] The molar ratio of the compound 2 to the base and the copper salt is 1:(1-4):(0.01-0.1), preferably 1:(2-3):(0.03-0.06).

[0038] Preferably, S2 satisfies at least one of the following conditions:

[0039] The base is selected from one or more of sodium bicarbonate, potassium bicarbonate, potassium carbonate, sodium carbonate, pyridine, and triethylamine, preferably potassium carbonate;

[0040] The copper salt is selected from one or more of cuprous iodide, cuprous bromide, cuprous chloride, cuprous oxide, cupric acetate, cupric chloride, cupric bromide, and cupric iodide, preferably cuprous chloride;

[0041] The solvent is ethylene glycol.

[0042] Preferably, the T2 temperature is 80-180°C, preferably 100-140°C.

[0043] Preferably, S3 satisfies at least one of the following conditions:

[0044] The mass volume ratio of the compound of formula 3 and the solvent is 1g:(2-10)ml, preferably 1:(6-8);

[0045] The molar ratio of the compound of formula 3, the sulfonylating agent and the base is 1:(1-2):(1-5), preferably 1:(1-1.5):(2-3).

[0046] Preferably, S3 satisfies at least one of the following conditions:

[0047] The base is selected from one or more of sodium bicarbonate, potassium bicarbonate, potassium carbonate, sodium carbonate, pyridine, and triethylamine, preferably triethylamine;

[0048] The sulfonylating agent is selected from one or more of methanesulfonyl chloride, methanesulfonic anhydride, and methanesulfonic acid, preferably methanesulfonyl chloride;

[0049] T3 temperature is 0-80°C, preferably 20-40°C;

[0050] The crystallization solvent is selected from one or more of methanol, ethanol and acetone, preferably methanol.

[0051] Preferably, in S3, the solvent is selected from one of dichloromethane, dichloroethane and ethyl acetate, preferably dichloroethane;

[0052] In another aspect, the present invention provides 2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate obtained by the preparation method described in the first aspect, wherein the structural formula of the 2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate is as follows:

[0053]

[0054] (III) Beneficial effects

[0055] The present invention provides a 2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate and a preparation method thereof. Compared with the prior art, the present invention has the following beneficial effects:

[0056] The present invention can obtain the final product 2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate through only three steps of chemical reaction. Compared with the prior art, the present invention has a novel synthesis route, fewer reaction steps, and the raw materials and reagents used in the reaction are cheap and easy to obtain, and no expensive palladium catalyst and dangerous reagents are needed. The present invention is green and environmentally friendly, the reaction conditions are temperature-controllable, the operation is simple, the product purity is high, the yield is high, and the product is suitable for industrial production. The present invention has broad prospects and industrial application value. DETAILED DESCRIPTION

[0057] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention are clearly and completely described. 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.

[0058] In order to better understand the above technical solution, the above technical solution will be described in detail below in conjunction with specific implementation methods.

[0059] Example 1

[0060] This embodiment provides a method for preparing 2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate, which specifically comprises the following steps:

[0061] S1. Synthesis of compounds of formula 2

[0062] At room temperature, o-bromophenol (17.3 g, 0.1 mol of compound 1) was dissolved in 100 mL of DMF, potassium carbonate (27.7 g, 0.2 mol) and trifluoroethyl p-toluenesulfonate (21.8 g, 0.1 mol) were added in sequence under stirring, and the temperature was raised to 100°C for 24 h. HPLC detected that the raw material had reacted completely, 200 ml of water was added, and 250 mL of EA was added for extraction. After separation, the organic layer was washed once with 100 mL of saturated brine, concentrated and dried to obtain a light yellow oily substance, which was compound 2, 24.8 g, with a purity of 99.1% and a yield of 97.3%.

[0063] The reaction equation is as follows:

[0064]

[0065] S2. Synthesis of compounds of formula 3

[0066] At room temperature, the compound of formula 2 (25.5 g, 0.1 mol) was dissolved in 150 mL of ethylene glycol, potassium carbonate (27.6 g, 0.2 mol) and cuprous chloride (0.3 g, 0.003 mol) were added under stirring, and the reaction was carried out at 100 ° C for 24 h. After the reaction, the mixture was cooled to room temperature, 200 ml of water was added, and 250 ml of EA was extracted. After separation, the organic layer was washed once with 100 mL of saturated brine, and finally concentrated and dried to obtain a colorless liquid, 22.1 g of the compound of formula 3, with a purity of 99.4% and a yield of 93.3%;

[0067] The reaction equation is as follows:

[0068]

[0069] S3. Synthesis of compounds of formula 4

[0070] At room temperature, the compound of formula 3 (23.6 g, 0.1 mol) was dissolved in 140 mL of dichloromethane, and then triethylamine (20.2 g, 0.2 mol) and methylsulfonyl chloride (12.6 g, 0.11 mol) were added dropwise. After the addition, the temperature was raised to 35°C and stirred for 6 h. After the reaction was completed by HPLC, 100 ml of saturated ammonium chloride water was added dropwise to quench, and the mixture was extracted with 250 ml of EA, washed once with saturated NaHCO3 solution, washed twice with saturated brine, and then dried. Most of the solvent was concentrated, 40 ml of methanol was added, and crystallization was carried out at 0°C for 10 h. After filtering, the mixture was dried at 55°C to obtain a solid compound of formula 4, (2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate) 31.1 g, with a yield of 99.0% and a purity of 99.6%.

[0071] The reaction equation is as follows:

[0072]

[0073] Example 2

[0074] S1. Synthesis of compounds of formula 2

[0075] At room temperature, o-chlorophenol (12.9 g, 0.1 mol of compound 1) was dissolved in 100 mL of DMAC, and sodium bicarbonate (25.2 g, 0.3 mol) and trifluoroethanol (15 g, 0.15 mol) were added in sequence under stirring, and the temperature was raised to 140°C for 20 h. After HPLC detection, the reaction of the raw material was complete, 200 ml of water was added, and 250 mL of EA was added for extraction. After separation, the organic layer was washed once with 100 mL of saturated brine, and finally concentrated and dried to obtain 20.4 g of compound 2 as a light yellow oil with a purity of 99.0% and a yield of 97%.

[0076] The reaction equation is as follows:

[0077]

[0078] S2. Synthesis of compounds of formula 3

[0079] At room temperature, the compound of formula 2 (21 g, 0.1 mol) was dissolved in 170 mL of ethylene glycol, and sodium carbonate (31.8 g, 0.3 mol) and cuprous bromide (0.86 g, 0.006 mol) were added under stirring conditions, and the reaction was carried out at 140° C. for 18 h. After the reaction was completed, the mixture was cooled to room temperature, 200 ml of water was added, and 250 ml of EA was used for extraction. After separation, the organic layer was washed once with 100 mL of saturated brine, and finally concentrated and dried to obtain 22.0 g of a colorless liquid compound of formula 3 with a purity of 99.2% and a yield of 93.1%.

[0080] The reaction equation is as follows:

[0081]

[0082] S3. Synthesis of compounds of formula 4

[0083] At room temperature, the compound of formula 3 (23.6 g, 0.1 mol) was dissolved in 190 mL of dichloroethane, and then potassium carbonate (41.5 g, 0.3 mol) and methylsulfonic anhydride (26.1 g, 0.15 mol) were added dropwise. After the addition, the temperature was raised to 40°C and stirred for reaction for 8 h. After the reaction was completed by HPLC detection, 100 ml of saturated ammonium chloride water was added dropwise to quench, and the mixture was extracted with 250 ml of EA, washed once with saturated NaHCO3 solution, washed twice with saturated brine, and dried. Most of the solvent was concentrated, 40 ml of ethanol was added, and crystallization was carried out at 0°C for 12 h. After filtration, the mixture was dried at 55°C to obtain 31.0 g of a solid compound of formula 4 (2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate), with a yield of 98.5% and a purity of 99.3%.

[0084] The reaction equation is as follows:

[0085]

[0086] Example 3

[0087] S1. Synthesis of compounds of formula 2

[0088] At room temperature, o-iodophenol (22.0 g of compound 1, 0.1 mol) was dissolved in 150 mL of NMP, triethylamine (25.3 g, 0.25 mol) and trifluoroethyl methanesulfonate (23.2 g, 0.13 mol) were added in sequence under stirring, and the temperature was raised to 120° C. for 28 h of heat preservation; HPLC detected that the raw material reaction was complete, 200 ml of water was added, and 250 mL of EA was added for extraction, and after separation, the organic layer was washed once with 100 mL of saturated brine, and finally concentrated and dried to obtain 29.2 g of compound 2 as a light yellow oil, with a purity of 99.1% and a yield of 96.7%;

[0089] The reaction equation is as follows:

[0090]

[0091] S2. Synthesis of compounds of formula 3

[0092] At room temperature, the compound of formula 2 (30.2 g, 0.1 mol) was dissolved in 210 mL of ethylene glycol, potassium bicarbonate (25.0 g, 0.25 mol) and copper acetate (0.91 g, 0.005 mol) were added under stirring, and the mixture was reacted at 120° C. for 22 h. After the reaction, the mixture was cooled to room temperature, 200 ml of water was added, and 250 ml of EA was used for extraction. After separation, the organic layer was washed once with 100 mL of saturated brine, and finally concentrated and dried to obtain 21.9 g of a colorless liquid compound of formula 3 with a purity of 99.3% and a yield of 92.7%.

[0093] The reaction equation is as follows:

[0094]

[0095] S3. Synthesis of compounds of formula 4

[0096] At room temperature, the compound of formula 3 (23.6 g, 0.1 mol) was dissolved in 160 mL of ethyl acetate, and then pyridine (19.8 g, 0.25 mol) was added, and methanesulfonic acid (12.5 g, 0.13 mol) was added dropwise. After the addition, the temperature was raised to 30°C and stirred for reaction for 8 h. After the reaction was completed by HPLC detection, 100 ml of saturated ammonium chloride water was added dropwise to quench, and the mixture was extracted with 250 ml of EA, washed once with saturated NaHCO3 solution, washed twice with saturated brine, and then dried. Most of the solvent was concentrated, 50 ml of acetone was added, and crystallization was carried out at 0°C for 10 h. After filtering, the mixture was dried at 55°C to obtain 30.8 g of a solid compound of formula 4 (2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate), with a yield of 98.0% and a purity of 99.0%.

[0097] The reaction equation is as follows:

[0098]

[0099] Example 4

[0100] S1. Synthesis of compounds of formula 2

[0101] At room temperature, o-iodophenol (22.0 g, 0.1 mol of compound 1) was dissolved in 130 mL of DMF, and pyridine (20.2 g, 0.3 mol) and trifluoroethyl methanesulfonate (23.2 g, 0.13 mol) were added in sequence under stirring, and the temperature was raised to 120°C for 20 h. HPLC detected that the raw material had reacted completely, 200 ml of water was added, and 250 mL of EA was added for extraction. After separation, the organic layer was washed once with 100 mL of saturated brine, and finally concentrated and dried to obtain 28.7 g of compound 2 as a light yellow oil with a purity of 98.5% and a yield of 95.0%.

[0102] The reaction equation is as follows:

[0103]

[0104] S2. Synthesis of compounds of formula 3

[0105] At room temperature, the compound of formula 2 (30.2 g, 0.1 mol) was dissolved in 190 mL of ethylene glycol, and sodium carbonate (26.5 g, 0.25 mol) and cuprous iodide (0.6 g, 0.003 mol) were added under stirring conditions, and the mixture was reacted at 120° C. for 24 h. After the reaction, the mixture was cooled to room temperature, 200 ml of water was added, and 250 ml of EA was used for extraction. After separation, the organic layer was washed once with 100 mL of saturated brine, and finally concentrated and dried to obtain 21.0 g of a colorless liquid compound of formula 3 with a purity of 97.2% and a yield of 89.0%.

[0106] The reaction equation is as follows:

[0107]

[0108] S3. Synthesis of compounds of formula 4

[0109] At room temperature, the compound of formula 3 (23.6 g, 0.1 mol) was dissolved in 160 mL of dichloromethane, and then potassium bicarbonate (30 g, 0.3 mol) and methylsulfonic anhydride (26.1 g, 0.15 mol) were added dropwise. After the addition, the temperature was raised to 20°C and stirred for reaction for 8 h. After the reaction was completed by HPLC detection, 100 ml of saturated ammonium chloride water was added dropwise to quench, and the mixture was extracted with 250 ml of EA, washed once with saturated NaHCO3 solution, washed twice with saturated brine, and dried. Most of the solvent was concentrated, 40 ml of methanol was added, and crystallization was carried out at 0°C for 10 h. After filtration, the mixture was dried at 55°C to obtain 30.1 g of a solid compound of formula 4 (2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate) with a yield of 95.8%.

[0110] The reaction equation is as follows:

[0111]

[0112] In summary, compared with the prior art, the present invention has the following beneficial effects:

[0113] The invention provides a method for preparing 2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate. The method has readily available raw materials, is environmentally friendly, has a novel route, and has a short synthesis route. The prepared 2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate has good purity, high yield, and low cost.

[0114] It should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device. In the absence of further restrictions, the elements defined by the sentence "comprise a ..." do not exclude the existence of other identical elements in the process, method, article or device including the elements.

[0115] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

[0116] The present invention illustrates the detailed process flow of the present invention through the above-mentioned embodiments, but the present invention is not limited to the above-mentioned detailed process flow, that is, it does not mean that the present invention must rely on the above-mentioned detailed process flow to be implemented. Those skilled in the art should understand that any improvement of the present invention, equivalent replacement of various raw materials of the product of the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

Claims

1. A method for preparing 2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate, characterized in that: The preparation method comprises taking o-halogenphenol as a raw material, sequentially performing etherification, Ullmann coupling, and sulfonylation reactions to obtain 2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate; The synthetic route is: Wherein, X is selected from one of Cl, Br, and I, The preparation method comprises the following steps: S1, dissolving the compound of formula 1 in a solvent, adding an etherifying agent and a base, stirring and reacting at a temperature of T1, adding water to quench the reaction after the reaction is completed, extracting with an extractant, drying and concentrating to obtain a compound of formula 2; S2, dissolving the compound of formula 2 in a solvent, adding a base and a copper salt, heating to T2 for reaction, and after the reaction is completed, pouring water to quench, extracting with an extractant, filtering and drying to obtain a compound of formula 3; S3, dissolving the compound of formula 3 in a solvent, adding a base, dropping a sulfonylating agent, stirring and reacting at temperature T3, after the reaction is complete, cooling to room temperature, dropping an acid to quench, extracting with an extraction solvent, washing, drying, concentrating, and crystallizing with a crystallization solvent to obtain a compound of formula 4, i.e., 2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate.

2. The preparation method according to claim 1, characterized in that: S1 satisfies at least one of the following conditions: The mass volume ratio of the compound of formula 1 and the solvent is 1g: (2-10)ml; The molar ratio of the compound of formula 1, the etherification agent and the base is 1:(1-3):(2-5).

3. The preparation method according to claim 1, characterized in that: S1 satisfies at least one of the following conditions: The etherification agent is selected from one or more of trifluoroethanol, trifluoroethyl methanesulfonate, and trifluoroethyl p-toluenesulfonate; The base is selected from one or more of sodium bicarbonate, potassium bicarbonate, potassium carbonate, sodium carbonate, pyridine, and triethylamine; The solvent is selected from at least one of N,N-dimethylformamide, N,N-dimethylacetamide and N-methylpyrrolidone.

4. The preparation method according to claim 1, characterized in that: The T1 temperature is 80-180°C.

5. The preparation method according to claim 1, characterized in that: S2 satisfies at least one of the following conditions: The mass volume ratio of the compound of formula 2 and the solvent is 1g: (2-10)ml; The molar ratio of the compound 2 to the base and the copper salt is 1:(1-4):(0.01-0.1).

6. The preparation method according to claim 1, characterized in that: S2 satisfies at least one of the following conditions: The base is selected from one or more of sodium bicarbonate, potassium bicarbonate, potassium carbonate, sodium carbonate, pyridine, and triethylamine; The copper salt is selected from one or more of cuprous iodide, cuprous bromide, cuprous chloride, cuprous oxide, cupric acetate, cupric chloride, cupric bromide and cupric iodide; The solvent is ethylene glycol.

7. The preparation method according to claim 1, characterized in that: The T2 temperature is 80-180°C.

8. The preparation method according to claim 1, characterized in that: S3 satisfies at least one of the following conditions: The mass volume ratio of the compound of formula 3 and the solvent is 1g: (2-10)ml; The molar ratio of the compound of formula 3, the sulfonylating agent and the base is 1:(1-2):(1-5).

9. The preparation method according to claim 1, characterized in that: S3 satisfies at least one of the following conditions: The base is selected from one or more of sodium bicarbonate, potassium bicarbonate, potassium carbonate, sodium carbonate, pyridine, and triethylamine; The sulfonylating agent is selected from one or more of methanesulfonyl chloride, methanesulfonic anhydride, and methanesulfonic acid; T3 temperature is 0-80℃; The crystallization solvent is selected from one or more of methanol, ethanol and acetone; The solvent is selected from one of dichloromethane, dichloroethane and ethyl acetate.

10. 2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate obtained by the preparation method according to any one of claims 1 to 9, characterized in that: The structural formula of the 2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl methanesulfonate is shown below:

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