Preparation method of ethyl 2-fluoropropionyl acetate

Abstract

The present application belongs to the field of fluorine-containing fine chemicals, and specifically relates to a method for preparing ethyl 2-fluoropropionyl acetate. The method for preparing ethyl 2-fluoropropionyl acetate comprises the following steps: 2 / N 2 The mixed gas is continuously fed into the tubular channel containing the ethyl propionyl acetate solution at a certain speed, and F 2 / N 2 The reaction of the mixed gas to ethyl propionylate is completed, and the obtained reaction solution is cooled, output, extracted and dried, and the solvent is evaporated to obtain ethyl 2-fluoropropionylate; the solvent in the ethyl propionylate solution includes at least one of acetic acid, formic acid, trifluoroethanol, and acetonitrile; the inlet and outlet of the pipeline channel are both provided with gas ports. The preparation method has high reaction efficiency, high atomic utilization rate, low cost, high safety, and simple operation, so it is more suitable for large-scale industrial production.

Description

Technical Field

[0001] The present application belongs to the field of fluorine-containing fine chemicals, and specifically relates to a method for preparing ethyl 2-fluoropropionyl acetate. Background Art

[0002] Ethyl 2-fluoropropionyl acetate is an important fluorine-containing organic intermediate and an important raw material for the synthesis of triazole antifungal drug fluliconazole and anti-HIV and anti-tuberculosis drug tetracyclic bipyranocoumarin.

[0003] At present, the method for producing ethyl 2-fluoropropionyl acetate that is widely used in industry is the route of condensing ethyl 2-fluoro-acetate and propionyl chloride under strong base. For example, CN200910224742 discloses a method for obtaining ethyl 2-fluoropropionyl acetate by acylation reaction in the presence of sodium ethoxide using ethyl fluoroacetate and propionyl chloride as raw materials (synthetic route 1). The disadvantage of this method is that sodium ethoxide, a strong base that is easily hydrolyzed, is used in the reaction. In addition, the reaction yield is low, only 30%, and propionyl chloride is easily decomposed to produce corrosive gas, which causes great damage to equipment and is not conducive to industrial production.

[0004] ,

[0005] Synthetic route 1

[0006] Chinese patent application CN110903194 A discloses another method for synthesizing ethyl 2-fluoropropionyl acetate compound, which uses ethyl 2-fluoropropionyl acetate and propionyl chloride as raw materials, first generates crude ethyl 2-fluoropropionyl acetate under the action of strong base sodium hydrogen, then adds boric acid and acetic anhydride for purification, and obtains pure product after distillation (synthetic route 2). This method uses strong base sodium hydrogen and highly corrosive acetic anhydride, and acetic anhydride is a controlled product that is easy to make drugs, so the production cost is high, the reaction process is highly corrosive, and it is not easy to industrialize.

[0007] ,

[0008] Synthetic route 2

[0009] Chinese patent application CN103664584 discloses a method for synthesizing ethyl 2-fluoropropionylacetate by reacting propionylacetate with sulfonyl chloride. The method firstly reacts propionylacetate with sulfonyl chloride to generate ethyl 2-chloropropionylacetate, and then uses potassium fluoride or sodium fluoride at 130 °C to obtain a 2-chloropropionylacetate. o C to replace the chlorine atom to generate ethyl 2-fluoropropionyl acetate (synthetic route 3). Although the raw materials of this method are convenient and easy to obtain, there are many by-products and the reaction temperature is high, which is not suitable for large-scale industrial production.

[0010] ,

[0011] Synthetic route 3

[0012] Chinese patent application CN107673967 discloses a kettle reaction method for synthesizing ethyl 2-fluoropropionyl acetate compound from 1-fluoro-2-butanone and carbonate. Under the action of a strong base (such as sodium hydrogen or sodium alcoholate), 1-fluoro-2-butanone and carbonate are condensed to synthesize ethyl 2-fluoropropionyl acetate (synthetic route 4). This method uses a strong base as a condensing agent, requires anhydrous conditions for the reaction, has high production costs, is complex in process, and has low safety. Therefore, this method is not suitable for large-scale industrial production.

[0013] ,

[0014] Synthetic route 4

[0015] Chinese patent application CN116143627 discloses another method for synthesizing ethyl 2-fluoropropionyl acetate compound, wherein a strong base is added to diethyl fluoromalonate to obtain potassium monoethyl malonate, and then propionyl chloride is added to the potassium salt, and ethyl 2-fluoropropionyl acetate is obtained after subsequent treatment (synthetic route 5). The method reported in the patent has many by-products, and a large amount of potassium salt is used in the reaction process, the production cost is high, and the process is complicated, so the method is not suitable for large-scale industrial production.

[0016] ,

[0017] Synthetic route 5

[0018] Chinese patent application CN200310108345 discloses another method for synthesizing ethyl 2-fluoropropionyl acetate compound: ethyl 2-fluoropropionyl acetate is obtained by alcoholysis, saponification, condensation and other multi-step reactions (synthetic route 6) using ethyl 2,2,3,3-tetrafluoropropionate as raw material. The method described in the patent has a long route, a complex process, a low yield, and the raw material ethyl 2,2,3,3-tetrafluoropropionate is not easy to obtain. The propionyl chloride used in the acylation reaction is very harmful to the equipment, which is not conducive to industrial production.

[0019] ,

[0020] Synthetic route 6

[0021] Org. Lett.2021, 23, 2811-2815 discloses a method for synthesizing ethyl 2-fluoropropionyl acetate compound. The method uses ethyl propionyl acetate as raw material and electrophilic fluorine reagent Selectfluor as fluorination reagent, and obtains ethyl 2-fluoropropionyl acetate after fluorination in acetonitrile (synthetic route 7). The fluorination reagent used in this method is very expensive, and a large amount of solid waste will be generated after the reaction, the atomic utilization rate is low, and the production cost is high. Therefore, this method is not suitable for large-scale industrial production.

[0022] ,

[0023] Synthetic route 7

[0024] J.Org.Chem . 1991, 56, 273-277 discloses another method for synthesizing ethyl 2-fluoropropionyl acetate. The reaction described in the document uses a flammable and explosive n-butyl lithium reagent. The reaction requires a temperature of -78 o C (Synthetic Route 8), the reaction operation is complicated and the production cost is high, so this method is not suitable for large-scale industrial production.

[0025] ,

[0026] Synthetic route 8

[0027] It can be seen from the above existing methods for preparing ethyl 2-fluoropropionyl acetate that the above methods are not suitable for large-scale industrial production due to various problems, such as complex operation, high requirements for the reaction environment, complex and expensive materials, low yield, etc. Summary of the invention

[0028] The purpose of the present application is to provide a method for preparing ethyl 2-fluoropropionyl acetate, which can improve the yield of ethyl 2-fluoropropionyl acetate, and the preparation method has high reaction efficiency, high atom utilization, low cost, high safety, and simple operation, so that it is more easily applicable to large-scale industrial production.

[0029] This application uses stable, readily available, and inexpensive ethyl propionylacetate and low molecular weight carboxylic acid compounds as raw materials, and a fluorine / nitrogen (F2 volume accounts for 3% to 20%) mixed gas as a fluorination reagent, and uses continuous flow technology (non-kettle reaction) to produce ethyl 2-fluoropropionylacetate. This method has the advantages of low raw material cost, simple operation, continuous and efficient reaction, and high degree of automation. The use of continuous flow technology greatly reduces the problem of strong heat release in the reaction, and fundamentally solves the potential safety problems in the use of fluorine gas. The synthesis route of this application is as follows:

[0030] .

[0031] To solve the above problems, the first solution provided in the present application is: a method for preparing ethyl 2-fluoropropionyl acetate, comprising the following steps:

[0032] The F2 / N2 mixed gas is continuously fed into the tubular channel containing the ethyl propionyl acetate solution at a certain speed, and the F2 / N2 mixed gas is continuously fed until the ethyl propionyl acetate is completely reacted, and the obtained reaction solution is cooled, output, extracted and dried, and the solvent is evaporated to obtain ethyl 2-fluoropropionyl acetate;

[0033] The solvent in the ethyl propionyl acetate solution includes at least one of acetic acid, formic acid, trifluoroethanol, and acetonitrile;

[0034] The inlet and the outlet of the tubular passage are both provided with gas openings.

[0035] Optionally, the tubular channel is formed into a plurality of curved structures.

[0036] Optionally, the ethyl propionylacetate solution is preheated before being input into the tubular channel.

[0037] Optionally, the preheating temperature is controlled at 40°C~50°C.

[0038] Optionally, the volume proportion of fluorine gas in the F2 / N2 mixed gas is 3% to 20%.

[0039] Optionally, the volume proportion of fluorine gas in the F2 / N2 mixed gas is 10%.

[0040] Optionally, the mass ratio of the ethyl propionylacetate to the low molecular weight carboxylic acid compound is 1:(1-10).

[0041] Optionally, the mass ratio of the ethyl propionylacetate to the solvent is 1:5.

[0042] Optionally, the reaction temperature is controlled at 35°C~50°C.

[0043] Optionally, the outer diameter of the tubular channel is 3 mm to 5 mm.

[0044] The present invention aims to provide a flow reaction process for synthesizing ethyl 2-fluoropropionyl acetate, which has the characteristics of high reaction efficiency, high atomic utilization rate, low cost, high safety and easy to realize automatic reaction. The technical scheme adopted by the present invention is: in a flow reactor, a low molecular weight compound is used as a solvent, and a fluorine gas direct fluorination method is used under room temperature conditions to directly introduce fluorine atoms on ethyl propionyl acetate, which is characterized in that the fluorine gas contacts and reacts with the ethyl propionyl acetate dissolved in the solvent under a flowing state, and the reaction time is short, and the selectivity and safety are high. Furthermore, the present application utilizes continuously input fluorine gas to contact ethyl propionyl acetate, and the contact time of any fluorine gas molecule with ethyl propionyl acetate is relatively short, and because the gas is continuously input and output, the heat generated by the reaction itself will be taken away, which not only ensures safe use, but also can maintain the reaction temperature within a certain range. In addition, the method has high atomic utilization rate, low cost, good reaction continuity (the kettle reaction needs to clean up the corresponding equipment after one reaction, and the present application can output the mixed solution obtained after the reaction and continue the next fluidized reaction), and high safety.

[0045] Flow chemistry is also called continuous flow chemistry. Its main feature is that chemical reactions are carried out in continuously flowing fluids. Its process methods are increasingly widely used in the field of synthesis. In flow chemical reactions, two or more different reaction materials are first pumped into a chamber, tube or microreactor at a given flow rate to react, and then the fluid containing the produced compounds is collected at the outlet. This process requires only a small amount of material and greatly improves process safety. Due to the inherent design of continuous flow technology, reaction conditions that cannot be safely achieved by batch reactions (such as kettle reactions) can be achieved, while eliminating the differences in products between batches. It has the advantages of higher product quality, fewer impurities, and faster reaction cycle time. Therefore, microchannel reactors are generally used for thermally violent reactions, dangerous chemical reactions, high temperature and high pressure reactions, etc. Therefore, the present application uses a microchannel reactor to optimize the method for fluorination of ethyl propionyl acetate using fluorine gas / nitrogen as raw materials. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] Figure 1 It is a process flow chart of the preparation method of ethyl 2-fluoropropionyl acetate of the present application;

[0047] Figure 2 It is a schematic diagram of the tubular channel of the reaction zone of the present application;

[0048] Figure 3 The gas chromatography and corresponding analysis results of ethyl 2-fluoropropionyl acetate synthesized in Example 1-control;

[0049] Figure 4 The gas chromatography and corresponding analysis results of ethyl 2-fluoropropionyl acetate synthesized in Example 2 of the present application;

[0050] Figure 5 The gas chromatography and corresponding analysis results of ethyl 2-fluoropropionyl acetate synthesized in Example 3 of the present application;

[0051] Figure 6 The gas chromatography and corresponding analysis results of ethyl 2-fluoropropionyl acetate synthesized in Example 4 of the present application;

[0052] Figure 7 The gas chromatography and corresponding analysis results of ethyl 2-fluoropropionyl acetate synthesized in Example 5 of the present application;

[0053] Figure 8 The gas chromatography and corresponding analysis results of ethyl 2-fluoropropionyl acetate synthesized in Example 6 of the present application;

[0054] Fig. 9 The gas chromatography and corresponding analysis results of ethyl 2-fluoropropionyl acetate synthesized in Example 7 of the present application;

[0055] Fig.10 The gas chromatography and corresponding analysis results of ethyl 2-fluoropropionyl acetate synthesized in Example 8 of the present application;

[0056] Fig.11 The gas chromatography and corresponding analysis results of ethyl 2-fluoropropionyl acetate synthesized in Example 9 of the present application. DETAILED DESCRIPTION

[0057] In order to make the purpose, technical scheme and advantages of the embodiments of the present application clearer, the technical scheme in the embodiments of the present application will be clearly and completely described below in combination with the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, rather than all the embodiments. The components of the embodiments of the present application described and shown herein can be arranged and designed in various different configurations.

[0058] The following are detailed examples:

[0059] Example 1 - Control

[0060] Process flow such as Figure 1 As shown, the preheating zone is 1.2 m long, the reaction zone is a tubular channel with gas ports and liquid baffles at both ends, the reaction zone is 25 m long, the outer diameter of the reaction zone is 3 mm, and the cooling zone is 1.3 m long. 20 g of ethyl propionyl acetate is pumped into the preheating zone at a flow rate of 20 mL / min using a plunger pump, preheated to 50 ° C, and then enters the reaction zone (such as Figure 2 The tubular channel with a curved structure as shown in the figure has gas openings at the inlet and outlet. 3 / h speed to introduce F2 / N2 mixed gas (fluorine gas accounts for 10% by volume in the F2 / N2 mixed gas), control the reaction temperature to 35℃~50℃, carry out fluorination reaction in the reaction zone, and stop ventilation after monitoring the reaction of the raw materials at the outlet of the reaction zone by GC. The reaction solution is cooled and output to obtain a crude product, to which saturated brine is added, and the liquid is extracted with ethyl acetate after filtration, the organic phases are combined, dried over anhydrous sodium sulfate, and ethyl acetate is removed by rotary evaporation to obtain a light yellow product. According to GC analysis and yield calculation, the content of ethyl 2-fluoropropionyl acetate in this embodiment is 51.3%, and the yield is 57%. Figure 3 shown.

[0061] Example 2

[0062] Process flow such as Figure 1 As shown, the preheating zone is 1.2 m long, the reaction zone is a tubular channel with gas ports and liquid baffles at both ends, the reaction zone is 25 m long, the outer diameter of the reaction zone is 3 mm, and the cooling zone is 1.3 m long. 120 g of ethyl propionyl acetate solution (the mass ratio of ethyl propionyl acetate to acetic acid is 1:5) is pumped into the preheating zone at a flow rate of 20 mL / min using a plunger pump, the ethyl propionyl acetate solution is preheated to 50 °C, and then enters the reaction zone (such as Figure 2 The tubular channel with a curved structure as shown in the figure has gas openings at the inlet and outlet. 3 / h rate of F2 / N2 mixed gas (fluorine gas accounts for 10% by volume in the F2 / N2 mixed gas), the reaction temperature is controlled to be 35°C~50°C, and the fluorination reaction is carried out in the reaction zone. The ventilation is stopped after the reaction of the raw materials at the outlet of the reaction zone is monitored by GC. The reaction solution is cooled and output, and the solvent is evaporated to obtain a crude product. Saturated brine is added thereto, and the liquid is extracted with ethyl acetate after filtration. The organic phases are combined, dried over anhydrous sodium sulfate, and ethyl acetate is removed by rotary evaporation to obtain a light yellow product. According to GC analysis and yield calculation, the content of ethyl 2-fluoropropionyl acetate in this embodiment is 94.1%, and the yield is 87%. Figure 4 shown.

[0063] Example 3

[0064] Process flow such as Figure 1 As shown, the preheating zone is 1.2 m long, the reaction zone is a tubular channel with gas ports and liquid baffles at both ends, the reaction zone is 25 m long, the outer diameter of the reaction zone is 3 mm, and the cooling zone is 1.3 m long. 120 g of ethyl propionyl acetate solution (the mass ratio of ethyl propionyl acetate to formic acid is 1:5) is pumped into the preheating zone at a flow rate of 20 mL / min using a plunger pump, and the ethyl propionyl acetate solution is preheated to 50 ° C, and then enters the reaction zone (such as Figure 2 The tubular channel with a curved structure as shown in the figure has gas openings at the inlet and outlet. 3 / h speed to introduce F2 / N2 mixed gas (fluorine gas accounts for 10% by volume in the F2 / N2 mixed gas), control the reaction temperature to 35°C~50°C, carry out fluorination reaction in the reaction zone, and stop ventilation after monitoring the reaction of the raw materials at the outlet of the reaction zone by GC. The reaction solution is cooled and output, and the solvent is evaporated to obtain a crude product, to which saturated brine is added, and the liquid is extracted with ethyl acetate after filtration, and the organic phases are combined, dried over anhydrous sodium sulfate, and ethyl acetate is removed by rotary evaporation to obtain a light yellow product. According to GC analysis and yield calculation, the content of ethyl 2-fluoropropionyl acetate in this embodiment is 94.9%, and the yield is 77%. Figure 5 shown.

[0065] Example 4

[0066] Process flow such as Figure 1 As shown, the preheating zone is 1.2 m long, the reaction zone is a tubular channel with gas ports and liquid baffles at both ends, the reaction zone is 25 m long, the outer diameter of the reaction zone is 3 mm, and the cooling zone is 1.3 m long. 120 g of ethyl propionyl acetate solution (the ratio of ethyl propionyl acetate to trifluoroethanol is 1:5) is pumped into the preheating zone at a flow rate of 20 mL / min using a plunger pump, the ethyl propionyl acetate solution is preheated to 50 °C, and then enters the reaction zone (such as Figure 2 The tubular channel with a curved structure as shown in the figure has gas openings at the inlet and outlet. 3 / h rate of F2 / N2 mixed gas (fluorine gas accounts for 10% by volume in the F2 / N2 mixed gas), the reaction temperature is controlled to be 35°C~50°C, and the fluorination reaction is carried out in the initial mixed solution. The ventilation is stopped after the reaction of the raw materials at the outlet of the reaction zone is monitored by GC. The reaction solution is cooled and output, and the solvent is evaporated to obtain a crude product. Saturated brine is added thereto to quench. After filtration, the liquid is extracted with ethyl acetate, the organic phases are combined, dried over anhydrous sodium sulfate, and ethyl acetate is removed by rotary evaporation to obtain a light yellow product. According to GC analysis and yield calculation, the content of ethyl 2-fluoropropionyl acetate in this embodiment is 93.9%, and the yield is 79%. Figure 6 shown.

[0067] Example 5

[0068] Process flow such as Figure 1 As shown, the preheating zone is 1.2 m long, the reaction zone is a tubular channel with gas ports and liquid baffles at both ends, the reaction zone is 25 m long, the outer diameter of the reaction zone is 3 mm, and the cooling zone is 1.3 m long. 120 g of ethyl propionyl acetate solution (the mass ratio of ethyl propionyl acetate to acetonitrile is 1:5) is pumped into the preheating zone at a flow rate of 20 mL / min using a plunger pump, the ethyl propionyl acetate solution is preheated to 50 °C, and then enters the reaction zone (such as Figure 2 The tubular channel with a curved structure as shown in the figure has gas openings at the inlet and outlet. 3 / h speed to introduce F2 / N2 mixed gas (fluorine gas accounts for 10% by volume in the F2 / N2 mixed gas), control the reaction temperature to 35°C~50°C, carry out fluorination reaction in the reaction zone, and stop ventilation after monitoring the reaction of the raw materials at the outlet of the reaction zone by GC. The reaction solution is cooled and output, and the solvent is evaporated to obtain a crude product, to which saturated brine is added for quenching, and the liquid is extracted with ethyl acetate after filtration. The organic phases are combined, dried over anhydrous sodium sulfate, and ethyl acetate is removed by rotary evaporation to obtain a light yellow product. According to GC analysis and yield calculation, the content of ethyl 2-fluoropropionyl acetate in this embodiment is 81.1%, and the yield is 81%. Figure 7 shown.

[0069] Example 6

[0070] Process flow such as Figure 1 As shown, the preheating zone is 1.2 m long, the reaction zone is a tubular channel with gas ports and liquid baffles at both ends, the reaction zone is 25 m long, the outer diameter of the reaction zone is 5 mm, and the cooling zone is 1.3 m long. 120 g of ethyl propionyl acetate solution (the mass ratio of ethyl propionyl acetate to acetic acid is 1:1) is pumped into the preheating zone at a flow rate of 20 mL / min using a plunger pump, the ethyl propionyl acetate solution is preheated to 40 °C, and then enters the reaction zone (such as Figure 2 The tubular channel with a curved structure as shown in the figure has gas openings at the inlet and outlet. 3 / h speed to introduce F2 / N2 mixed gas (the volume proportion of fluorine gas in the F2 / N2 mixed gas is 3%), control the reaction temperature to 35℃~50℃, carry out fluorination reaction in the reaction zone, and stop ventilation after monitoring the reaction of the raw materials at the outlet of the reaction zone by GC. The reaction solution is cooled and output, and the solvent is evaporated to obtain a crude product, to which saturated brine is added for quenching, and the liquid is extracted with ethyl acetate after filtration. The organic phases are combined, dried over anhydrous sodium sulfate, and ethyl acetate is removed by rotary evaporation to obtain a light yellow product. According to GC analysis and yield calculation, the content of ethyl 2-fluoropropionyl acetate in this embodiment is 92.5%, and the yield is 89%. Figure 8 shown.

[0071] Example 7

[0072] Process flow such as Figure 1 As shown, the preheating zone is 1.2 m long, the reaction zone is a tubular channel with gas ports and liquid baffles at both ends, the reaction zone is 25 m long, the outer diameter of the reaction zone is 5 mm, and the cooling zone is 1.3 m long. 120 g of ethyl propionyl acetate solution (the mass ratio of ethyl propionyl acetate to acetic acid is 1:10) is pumped into the preheating zone at a flow rate of 20 mL / min using a plunger pump, the ethyl propionyl acetate solution is preheated to 45 °C, and then enters the reaction zone (such as Figure 2 The tubular channel with a curved structure as shown in the figure has gas openings at the inlet and outlet. 3 / h rate of introduction of F2 / N2 mixed gas (fluorine gas accounts for 20% by volume in the F2 / N2 mixed gas), the reaction temperature is controlled to be 35°C~50°C, and the fluorination reaction is carried out in the reaction zone. The ventilation is stopped after the reaction of the raw materials at the outlet of the reaction zone is monitored by GC. The reaction solution is cooled and output, and the solvent is evaporated to obtain a crude product, to which saturated brine is added for quenching. After filtration, the liquid is extracted with ethyl acetate, the organic phases are combined, dried over anhydrous sodium sulfate, and ethyl acetate is removed by rotary evaporation to obtain a light yellow product. According to GC analysis and yield calculation, the content of ethyl 2-fluoropropionyl acetate in this embodiment is 92.0%, and the yield is 88.6%. Fig. 9 shown.

[0073] Example 8

[0074] Process flow such as Figure 1 As shown, the preheating zone is 1.2 m long, the reaction zone is a tubular channel with gas ports and liquid baffles at both ends, the reaction zone is 25 m long, the outer diameter of the reaction zone is 3 mm, and the cooling zone is 1.3 m long. 300 g of ethyl propionyl acetate solution (the mass ratio of ethyl propionyl acetate to acetic acid is 1:2) is pumped into the preheating zone at a flow rate of 20 mL / min using a plunger pump, the ethyl propionyl acetate solution is preheated to 40 °C, and then enters the reaction zone (as shown in FIG. Figure 2 The tubular channel with a curved structure as shown in the figure has gas openings at the inlet and outlet. 3 / h rate of introduction of F2 / N2 mixed gas (fluorine gas accounts for 6% by volume in the F2 / N2 mixed gas), the reaction temperature is controlled to be 35°C~50°C, and the fluorination reaction is carried out in the reaction zone. The ventilation is stopped after the reaction of the raw materials at the outlet of the reaction zone is monitored by GC. The reaction solution is cooled and output, and the solvent is evaporated to obtain a crude product, to which saturated brine is added for quenching. After filtration, the liquid is extracted with ethyl acetate, the organic phases are combined, dried over anhydrous sodium sulfate, and ethyl acetate is removed by rotary evaporation to obtain a light yellow product. According to GC analysis and yield calculation, the content of ethyl 2-fluoropropionyl acetate in this embodiment is 81.0%, and the yield is 87.6%. Fig.10 shown.

[0075] Example 9

[0076] Process flow such as Figure 1 As shown, the preheating zone is 1.2 m long, the reaction zone is a tubular channel with gas ports and liquid baffles at both ends, the reaction zone is 25 m long, the outer diameter of the reaction zone is 3 mm, and the cooling zone is 1.3 m long. 30 kg of ethyl propionyl acetate solution (the mass ratio of ethyl propionyl acetate to acetic acid is 1:8) is pumped into the preheating zone at a flow rate of 20 mL / min using a plunger pump, the ethyl propionyl acetate solution is preheated to 45 °C, and then enters the reaction zone (such as Figure 2 The tubular channel with a curved structure as shown in the figure has gas openings at the inlet and outlet. 3 / h rate of F2 / N2 mixed gas (fluorine gas accounts for 15% by volume in the F2 / N2 mixed gas), the reaction temperature is controlled to be 35°C~50°C, and the fluorination reaction is carried out in the reaction zone. The ventilation is stopped after the reaction of the raw materials at the outlet of the reaction zone is monitored by GC. The reaction solution is cooled and output, and the solvent is evaporated to obtain a crude product, to which saturated brine is added for quenching. After filtration, the liquid is extracted with ethyl acetate, the organic phases are combined, dried over anhydrous sodium sulfate, and ethyl acetate is removed by rotary evaporation to obtain a light yellow product. According to GC analysis and yield calculation, the content of ethyl 2-fluoropropionyl acetate in this embodiment is 90.3%, and the yield is 87.6%. Fig.11 shown.

[0077] 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. The preparation method of ethyl 2-fluoropropionyl acetate is characterized in that: The following steps are included: The ethyl propionyl acetate solution is preheated and then fed into the tubular channel, and the F2 / N2 mixed gas is continuously fed into the tubular channel containing the ethyl propionyl acetate solution at a certain speed, and the F2 / N2 mixed gas is continuously fed until the ethyl propionyl acetate reacts completely, and the obtained reaction solution is cooled, output, extracted and dried, and the solvent is evaporated to obtain ethyl 2-fluoropropionyl acetate; The preheating temperature is controlled at 40°C to 50°C, and the reaction temperature is controlled at 35°C to 50°C; The solvent in the ethyl propionylate solution includes at least one of acetic acid, formic acid, trifluoroethanol, and acetonitrile, and the mass ratio of the ethyl propionylate to the solvent is 1:(1-10); The inlet and outlet of the tubular channel are both provided with gas openings, and the outer diameter of the tubular channel is 3 mm to 5 mm; The volume proportion of fluorine gas in the F2 / N2 mixed gas is 3% to 20%.

2. The preparation method according to claim 1, characterized in that: The tubular passage is formed into a plurality of curved structures.

3. The preparation method according to claim 1, characterized in that: The volume proportion of fluorine gas in the F2 / N2 mixed gas is 10%.

4. The preparation method according to claim 1, characterized in that: The mass ratio of the ethyl propionylacetate to the solvent is 1:5.

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