Preparation method of trifluoropropionate

Abstract

The invention discloses a preparation method of trifluoropropionate, which comprises the following steps: 1, dissolving alkyl acetate in tetrahydrofuran, dropwise adding a lithium diisopropylamide-tetrahydrofuran solution under the conditions of nitrogen protection and temperature not higher than-60 DEG C, and stirring for reaction after dropwise adding; 2, dropwise adding trimethylchlorosilane, and stirring for reaction; 3, quenching with ice water, extracting with a first organic solvent, washing with a saturated saline solution, drying, filtering and spin-drying to obtain a trimethyl [[1-(alkoxy) vinyl] oxy]-silane crude product; 4, dissolving the trimethyl [[1-(alkoxy) vinyl] oxy]-silane crude product in a second organic solvent, adding a catalyst and a trifluoromethylation reagent at the temperature of-10 DEG C to 0 DEG C under the protection of nitrogen, and after addition, recovering to room temperature for stirring reaction; the trifluoro methylation reagent is a Togni reagent I or a Togni reagent II, and the trifluoro methylation reagent is a trifluoro methylation reagent or a trifluoro methylation reagent or a trifluoro methylation reagent or a trifluoro methylation reagent. 5, adding water for quenching, extracting, drying and performing rotary evaporation to obtain a crude product, and passing through a column to obtain a product; the method has the advantages that the yield is high, the affinity to the environment is good, and the raw materials are easy to obtain.

Description

Technical Field

[0001] The invention relates to the technical field of organic fluoride synthesis, and in particular to a method for preparing trifluoropropionate. Background Art

[0002] Organic fluorides are highly valued in the field of organic synthesis due to their special physical and chemical properties, and are widely used in various disciplines and fields such as medicine, pesticides, surfactants, and battery additives. There are very few natural organic fluorides in nature, and most of them are synthesized artificially. However, the synthesis of organic fluorides still has certain technical difficulties, which greatly limits the practical application of such compounds.

[0003] Application CN102010333A discloses a method for preparing 3,3,3-trifluoropropionate. The method uses protonic acid and Lewis acid as catalysts, and trifluoropropenyl ether reacts with hydrogen peroxide. The disadvantage of the method is that the raw material trifluoropropenyl ether is difficult to obtain and is not easy to purchase.

[0004] Application CN 115784880A discloses a fluorine-containing carboxylic acid ester and a preparation method thereof. The method uses an activated acylating agent to react with an alcohol. The method has the disadvantages that the acylating agent needs to be prepared in advance and the preparation of the acylating agent causes great environmental pollution. Summary of the invention

[0005] The purpose of the present invention is to provide a method for preparing trifluoropropionate with readily available raw materials, simple preparation process, high yield and little environmental pollution.

[0006] To achieve the above-mentioned purpose, the technical scheme adopted by the present invention is: a method for preparing trifluoropropionate, comprising the following steps: 1. dissolving alkyl acetate in tetrahydrofuran (THF), under nitrogen protection, at a temperature not higher than -60°C, adding lithium diisopropylamide (LDA)-tetrahydrofuran solution dropwise, stirring and reacting after the addition is completed; 2. adding trimethylchlorosilane (TMSCl), stirring and reacting first, and then returning to room temperature and stirring and reacting; 3. quenching with ice water, extracting with a first organic solvent, washing with saturated brine, drying, filtering and spin-drying to obtain a crude trimethyl [[1-(alkoxy) vinyl] oxy]-silane; 4. dissolving the crude trimethyl [[1-(alkoxy) vinyl] oxy]-silane in a second organic solvent, adding a catalyst and a trifluoromethylating agent under nitrogen protection at a temperature of -10°C to 0°C, and then returning to room temperature and stirring and reacting; the trifluoromethylating agent is Tognireagent I or Togni Reagent II; 5. Quench with water, extract, dry and evaporate to obtain a crude product, and pass it through a column to obtain the product.

[0007] Alkyl acetates have the general average formula as follows: , The trifluoropropionate esters have the general average formula as follows: , In the above two formulas, R1 is a hydrocarbon group having 0 to 10 carbon atoms.

[0008] The schematic diagram of the above reaction process is as follows: .

[0009] Furthermore, in the aforementioned method for preparing trifluoropropionic ester, the concentration of lithium diisopropylamide in the lithium diisopropylamide-tetrahydrofuran solution is 2 mol / L.

[0010] Furthermore, in the aforementioned method for preparing trifluoropropionic ester, the molar ratio of the alkyl acetate to lithium diisopropylamide in the first step is 1:(1-1.5).

[0011] Furthermore, in the aforementioned method for preparing trifluoropropionic ester, the molar ratio of alkyl acetate to trimethylsilyl chloride is 1:(1.5-2).

[0012] Furthermore, in the aforementioned method for preparing trifluoropropionic ester, the first organic solvent is selected from one of n-hexane, cyclohexane, and petroleum ether; the first organic solvent is preferably n-hexane.

[0013] Furthermore, in the aforementioned method for preparing trifluoropropionic acid ester, in the fourth step, the second organic solvent is selected from dichloromethane or tetrahydrofuran, and the second organic solvent is preferably dichloromethane.

[0014] Furthermore, in the aforementioned method for preparing a trifluoropropionic ester, in which, in the fourth step, the catalyst is selected from one of bis(trifluoromethylsulfonyl)imide lithium, bis(trifluoromethylsulfonyl)imide copper, bis(trifluoromethylsulfonyl)imide zinc, and trimethylsilylbis(trifluoromethylsulfonyl)imide; and the molar ratio of trimethyl[[1-(alkoxy)vinyl]oxy]-silane to the catalyst is 1:(2.5% to 10%).

[0015] Furthermore, in the aforementioned method for preparing trifluoropropionate, the catalyst is trimethylsilylbis(trifluoromethylsulfonyl)imide.

[0016] Furthermore, in the aforementioned method for preparing a trifluoropropionate, the trifluoromethylation reagent is preferably Togni reagent II. The schematic diagram of Togni reagent is as follows: , .

[0017] Furthermore, in the aforementioned method for preparing trifluoropropionic ester, in the fifth step, dichloromethane is used for extraction.

[0018] The advantages of the present invention are: 1. A new preparation process for trifluoropropionate is provided, which has low purification difficulty, few by-products, high yield and good affinity to the environment. 2. The generated waste is easy to handle, the process route is simple, and the reaction is easy to control. 3. The raw materials are easy to obtain and can be directly purchased on the reagent website. Description of the drawings: Figure 1 is the C NMR spectrum of the product in Example 1; Figure 2 is the NMR F spectrum of the product in Example 1; Figure 3 It is the H NMR spectrum of the product in Example 1. DETAILED DESCRIPTION

[0020] The preparation method of the trifluoropropionic ester described in the present invention is described in detail below through specific examples.

[0021] Example 1: 100 mg of ethyl acetate was dissolved in 3 mL of THF solution. Under N2 protection, 0.7 mL of lithium diisopropylamide-tetrahydrofuran solution (2M in THF) was slowly added dropwise at -78 °C, and stirred for 1 h after the addition. 2. 185 mg of TMSCl was added dropwise and continued to stir for 1 h, and then the mixture was returned to room temperature and stirred for 1 h. 3. Ice water was quenched, hexane was extracted, saturated brine was washed, dried, filtered and spin-dried to obtain 155 mg of crude trimethyl[[1-(ethoxy)vinyl]oxy]-silane as an intermediate. 4. The crude trimethyl[[1-(ethoxy)vinyl]oxy]-silane was dissolved in 3 mL of dichloromethane. Under N2 protection, 17 mg of trimethylsilylbis(trifluoromethylsulfonyl)imide and 382 mg of Togni reagent II were added at -10 °C, and the reaction was returned to room temperature and stirred for 24 h. 5. Add water to quench, extract with DCM, dry and evaporate to obtain a crude product, and pass through a column to obtain 133 mg of the final product (yield: 75%). The product NMR C spectrum is shown in Figure 1 , NMR F spectrum see Figure 2 , NMR H spectrum see Figure 3 .

[0022] Example 2: 100 mg of methyl acetate was dissolved in 3 mL of tetrahydrofuran (THF), and 0.8 mL of lithium diisopropylamide-tetrahydrofuran solution (2M in THF) was slowly added dropwise at -78°C under N2 protection, and stirred for 1 hour after the addition; 220 mg of TMSCl was added dropwise and continued to stir for 1 hour, and then the mixture was returned to room temperature and stirred for 1 hour; 3. Ice water was quenched, petroleum ether was extracted, saturated brine was washed, dried, filtered and spin-dried to obtain 167 mg of crude trimethyl[[1-(methoxy)vinyl]oxy]-silane as an intermediate; 4. The crude trimethyl[[1-(methoxy)vinyl]oxy]-silane was dissolved in 3 mL of dichloromethane, and 20 mg of trimethylsilylbis(trifluoromethylsulfonyl)imide and 455 mg of Togni reagent II, then return to room temperature and stir to react for 24 hours; V. Add water to quench, extract with dichloromethane (DCM), dry and rotary evaporate to obtain a crude product, and pass through a column to obtain 138 mg of the final product (yield: 72%).

[0023] Example 3: 100 mg of propyl acetate was dissolved in 3 mL of THF solution. Under N2 protection, 0.6 mL of lithium diisopropylamide-tetrahydrofuran solution (2M in THF) was slowly added dropwise at -78 °C, and stirred for 1 h after the addition. 2. 160 mg of TMSCl was added dropwise and continued to stir for 1 h, and then the mixture was stirred at room temperature for 1 h. 3. The mixture was quenched with ice water, extracted with cyclohexane, washed with saturated brine, dried, filtered and spin-dried to obtain 145 mg of crude trimethyl[[1-(propoxy)vinyl]oxy]-silane as an intermediate. 4. The crude trimethyl[[1-(propoxy)vinyl]oxy]-silane was dissolved in 3 mL of dichloromethane. Under N2 protection, 8 mg of trimethylsilylbis(trifluoromethylsulfonyl)imide and 330 mg of Togni reagent II were added at -10 °C, and the mixture was stirred at room temperature for 24 h. 5. Add water to quench, extract with DCM, dry and evaporate to obtain a crude product, and pass through a column to obtain 116 mg of the final product (yield: 70%).

[0024] Example 4: 100 mg of butyl acetate was dissolved in 3 mL of THF. Under N2 protection, 0.5 mL of lithium diisopropylamide-tetrahydrofuran solution (2M in THF) was slowly added dropwise at -78 ° C. After the addition, stirring was continued for 1 h. 140 mg of TMSCl was added dropwise and continued to stir for 1 h. Then the mixture was returned to room temperature and stirred for 1 h. 3. Ice water was quenched, hexane was extracted, saturated brine was washed, dried, filtered and spin-dried to obtain 131 mg of crude intermediate trimethyl[[1-(butoxy)vinyl]oxy]-silane. 4. The crude trimethyl[[1-(butoxy)vinyl]oxy]-silane was dissolved in 3 mL of dichloromethane. Under N2 protection, 24 mg of trimethylsilylbis(trifluoromethylsulfonyl)imide and 276 mg of Togni reagent II were added at -10 ° C. The reaction was returned to room temperature and stirred for 24 h. 5. Add water to quench, extract with DCM, dry and evaporate to obtain a crude product, and pass through a column to obtain 98 mg of the final product (yield: 67%).

[0025] Example 5: 10g ethyl acetate was dissolved in 100mL THF solution, and 62mL lithium diisopropylamide-tetrahydrofuran solution (2M in THF) was slowly added at -78℃ under N2 protection, and stirred for 1h after the addition; 2. 18.5g TMSCl was added and continued to stir for 1h, and then the mixture was stirred at room temperature for 1h; 3. Ice water was quenched, hexane was extracted, saturated brine was washed, dried, filtered and dried to obtain 17g trimethyl [[1-(ethoxy) vinyl] oxy] - silane crude product; 4. The crude product was dissolved in 150mL tetrahydrofuran, and 1.9g trimethylsilyl bis (trifluoromethylsulfonyl) imide and 42g Togni reagent Ⅱ were added at -10℃ under N2 protection, and the mixture was stirred at room temperature for 24h. 5. Water was added to quench, DCM was extracted, and the crude product was dried and evaporated to obtain the crude product, which was passed through a column to obtain 12.8g of the final product (yield: 72%).

[0026] Example 6: 5g of ethyl acetate was dissolved in 100mL of THF solution. Under N2 protection, 31mL of lithium diisopropylamide-tetrahydrofuran solution (2M in THF) was slowly added at -78℃, and stirred for 1h after the addition. 2. 9.3g of TMSCl was added and continued to stir for 1h, and then the mixture was stirred at room temperature for 1h. 3. Ice water was quenched, hexane was extracted, saturated brine was washed, dried, filtered and spin-dried to obtain 8g of crude trimethyl [[1-(ethoxy) vinyl] oxy]-silane. 4. The crude product was dissolved in 150mL of tetrahydrofuran, and 0.9g of trimethylsilyl bis (trifluoromethylsulfonyl) imide and 21g of Togni reagent II were added at -10℃ under N2 protection, and the mixture was stirred at room temperature for 24h. 5. Water was added to quench, DCM was extracted, and the crude product was dried and evaporated to obtain the crude product, which was passed through a column to obtain 6.2g of the final product (yield: 70%).

[0027] Comparative Example 1: 100 mg of ethyl acetate was dissolved in 3 mL of THF solution. Under N2 protection, 0.7 mL of lithium diisopropylamide-tetrahydrofuran solution (2M in THF) was slowly added at -78 °C, and stirred for 1 h after the addition. 2. 185 mg of TMSCl was added and continued to stir for 1 h, and then the mixture was stirred at room temperature for 1 h. 3. The mixture was quenched with ice water, extracted with n-hexane, washed with saturated brine, dried, filtered and dried to obtain a crude intermediate of 160 mg of trimethyl[[1-(methoxy)vinyl]oxy]-silane. 4. The crude product was dissolved in dichloromethane, and under N2 protection, 31 mg of bis(trifluoromethylsulfonyl)imide zinc and 396 mg of Togni reagentⅡ were added at -10 °C, and the mixture was stirred at room temperature for 24 h. 5. The mixture was quenched with water, extracted with DCM, and dried and evaporated to obtain a crude product, which was passed through a column to obtain 103 mg of the final product (yield: 58%).

[0028] Comparative Example 2: 100 mg of ethyl acetate was dissolved in THF solution. Under N2 protection, 0.7 mL of lithium diisopropylamide-tetrahydrofuran solution (2M in THF) was slowly added dropwise at -78 °C, and stirred for 1 h after the addition. 2. 185 mg of TMSCl was added dropwise and continued to stir for 1 h, and then the mixture was returned to room temperature and stirred for 1 h. 3. Ice water was quenched, hexane was extracted, saturated brine was washed, dried, filtered and spin-dried to obtain 158 mg of crude trimethyl [[1-(methoxy) vinyl] oxy] - silane as an intermediate. 4. The crude trimethyl [[1-(methoxy) vinyl] oxy] - silane was dissolved in 3 mL of dichloromethane. Under N2 protection, 17 mg of trimethylsilyl bis (trifluoromethylsulfonyl) imide and 374 mg of Togni reagent I were added at -10 °C, and the mixture was returned to room temperature and stirred for 24 h. 5. Add water to quench, extract with DCM, dry and evaporate to obtain a crude product, and pass through a column to obtain 77 mg of the final product (yield: 43%).

[0029] It can be seen from the above examples that when the catalyst is bis(trifluoromethylsulfonyl)imide lithium, bis(trifluoromethylsulfonyl)imide copper, bis(trifluoromethylsulfonyl)imide zinc or the trifluoromethylation reagent is Togni reagent I, the yield is relatively low, while when trimethylsilyl bis(trifluoromethylsulfonyl)imide is used in combination with Togni reagent II, the yield is greatly improved.

[0030] The advantages of the present invention are: 1. A new preparation process for trifluoropropionate is provided, which has low purification difficulty, few by-products, high yield and good affinity to the environment. 2. The generated waste is easy to handle, the process route is simple, and the reaction is easy to control. 3. The raw materials are easy to obtain and can be directly purchased on the reagent website.

Claims

1. A method for preparing trifluoropropionate, comprising the following steps:

1. Dissolve alkyl acetate in tetrahydrofuran, under nitrogen protection, at a temperature not higher than -60°C, dropwise add lithium diisopropylamide-tetrahydrofuran solution, and stir to react after dropping; 2. Dropwise add trimethylchlorosilane and stir to react, then return to room temperature and stir to react; 3. Quench with ice water, extract with a first organic solvent, wash with saturated brine, dry, filter and spin dry to obtain a crude trimethyl[[1-(alkoxy)vinyl]oxy]-silane; 4. Dissolve the crude trimethyl[[1-(alkoxy)vinyl]oxy]-silane in a second organic solvent, under nitrogen protection, add a catalyst and a trifluoromethylation reagent at a temperature of -10°C to 0°C, and return to room temperature and stir to react after adding; the trifluoromethylation reagent is Togni reagentⅠ or Togni reagentⅡ; trimethyl[[1-(alkoxy)vinyl]oxy]- The molar ratio of silane to trifluoromethylation agent is 1:(1-1.5); 5. quenching with water, extracting, drying and rotary evaporating to obtain a crude product, and passing through a column to obtain a product; Alkyl acetates have the general average formula as follows: , The trifluoropropionic acid esters have the general average formula as follows: , In the formula, R1 is a hydrocarbon group having 1 to 10 carbon atoms.

2. The method for preparing a trifluoropropionic ester according to claim 1, characterized in that: The concentration of lithium diisopropylamide in the lithium diisopropylamide-tetrahydrofuran solution is 2 mol / L.

3. A method for preparing a trifluoropropionic ester according to claim 1 or 2, characterized in that: The molar ratio of the alkyl acetate to lithium diisopropylamide in the first step is 1:(1-1.5).

4. The method for preparing a trifluoropropionic ester according to claim 1, characterized in that: The molar ratio of alkyl acetate to trimethylsilyl chloride is 1:(1.5-2).

5. The method for preparing a trifluoropropionate according to claim 1, characterized in that: In the third step, the first organic solvent is selected from one of n-hexane, cyclohexane and petroleum ether.

6. The method for preparing a trifluoropropionic ester according to claim 1, characterized in that: In the fourth step, the second organic solvent is selected from dichloromethane or tetrahydrofuran.

7. The method for preparing a trifluoropropionic ester according to claim 1, characterized in that: In the fourth step, the catalyst is selected from one of bis(trifluoromethylsulfonyl)imide lithium, bis(trifluoromethylsulfonyl)imide copper, bis(trifluoromethylsulfonyl)imide zinc, and trimethylsilylbis(trifluoromethylsulfonyl)imide; the molar ratio of trimethyl[[1-(alkoxy)vinyl]oxy]-silane to the catalyst is 1:(2.5% to 10%).

8. The method for preparing a trifluoropropionate according to claim 6, characterized in that: in, The catalyst used is trimethylsilylbis(trifluoromethylsulfonyl)imide.

9. The method for preparing a trifluoropropionic ester according to claim 1 or 8, characterized in that: In the fourth step, the trifluoromethylation reagent is Togni reagent II.

10. The method for preparing a trifluoropropionic ester according to claim 1, characterized in that: A method for preparing trifluoropropionate comprises the following steps: in the fifth step, dichloromethane is used for extraction.

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