A process for the preparation of 3-(trifluoromethyl)cyclobutan-1-one

Abstract

The application discloses a preparation method of 3-(trifluoromethyl)cyclobutan-1-one and belongs to the technical field of organic synthesis. The method comprises the following steps: under an inert atmosphere, double ethylene ketone is cracked at 550 DEG C to 650 DEG C to generate ethylene ketone gas; under the conditions of the inert atmosphere and light, a cycloaddition reaction of the ethylene ketone gas and 1,1,1-trifluoropropene gas is carried out at a temperature of-50 DEG C to 0 DEG C to generate 3-(trifluoromethyl)cyclobutan-1-one; and the wavelength of the light source of the light is 250 nm to 650 nm. The raw materials of the method are all cheap and easily obtained bulk chemicals, no solvent and catalyst need to be added, the reaction condition is mild, the operation is simple, and the method is suitable for industrial production; and the obtained product 3-(trifluoromethyl)cyclobutan-1-one is an important pharmaceutical intermediate.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for preparing the pharmaceutical intermediate 3-(trifluoromethyl)cyclobutane-1-one. Background Technology

[0002] Compound 3-(trifluoromethyl)cyclobutane-1-one (Formula IV) is an important organic synthetic intermediate and a crucial building block for the synthesis of many active pharmaceutical molecules. Its structural formula (IV) is: Among them, patent WO 2024 / 233550 A1 involves the active molecules C71 / 74 / 75 of a 15-hydroxy-prostaglandin dehydrogenase inhibitor; patent WO 2024 / 141011 A1 involves the active molecule 111-P1 / 2 of a complement factor B inhibitor and its pharmaceutical composition; and patent CN 116903586 A involves the bioactive molecule 46-a / b of a reversibly binding BTK inhibitor developed for BTK (Bruton's tyrosine kinase) inhibitors. The synthesis of these drug molecules all involve this important organic synthetic intermediate, 3-(trifluoromethyl)cyclobutane-1-one.

[0003]

[0004] Currently, there are no literature or patent reports on the synthesis of this intermediate; its expensive price can only be found on the websites of some reagent vendors (such as Sigma Aldrich). Therefore, developing a method for preparing 3-(trifluoromethyl)cyclobutane-1-one is of great significance for the discovery of novel drug structures. Summary of the Invention

[0005] 1. Technical problem to be solved: To address the problems existing in the prior art, the technical problem to be solved by the present invention is to provide a method for preparing 3-(trifluoromethyl)cyclobutane-1-one, which uses readily available raw materials, is simple to operate, has mild reaction conditions, and is low in cost, making it suitable for industrial production.

[0006] 2. Technical Solution: To solve the above problems, the present invention adopts the following technical solution.

[0007] A method for preparing 3-(trifluoromethyl)cyclobutane-1-one includes the following steps: (1) Under an inert atmosphere, diketene is heated and decomposed to obtain ketene gas; (2) Under inert atmosphere and light conditions, the ketene gas obtained in step (1) undergoes a cycloaddition reaction with 1,1,1-trifluoropropylene to obtain the 3-(trifluoromethyl)cyclobutane-1-one.

[0008] In some embodiments of the present invention, the temperature of the heating pyrolysis in step (1) is 550°C to 650°C.

[0009] In some embodiments of the present invention, the illumination in step (2) uses a light source with a wavelength of 250nm to 650nm; further, the light source is an LED light source with a wavelength of 365nm to 450nm.

[0010] In some embodiments of the present invention, the temperature of the cycloaddition reaction in step (2) is -50°C to 0°C; further, the temperature is -30°C to -10°C.

[0011] In some embodiments of the present invention, the molar ratio of ketene to 1,1,1-trifluoropropylene in step (2) is 1:2 to 1:10.

[0012] In some embodiments of the present invention, step (1) specifically involves: evaporating diketene, passing it into a pyrolysis zone heated to 550°C to 650°C for pyrolysis, and condensing and collecting the generated ketene gas in a cold trap, wherein the temperature of the cold trap is below -50°C (e.g., using liquid nitrogen cooling).

[0013] In some embodiments of the present invention, the cycloaddition reaction in step (2) is carried out under conditions without the addition of an external solvent.

[0014] In some embodiments of the present invention, the preparation method further includes: purifying the reaction product obtained in step (2) by distillation (e.g., atmospheric distillation).

[0015] 3. Beneficial effects: Compared with the prior art, the technical solution provided by this invention has the following advantages: (1) The reaction raw materials, diketene and 1,1,1-trifluoropropylene, are both industrially available bulk chemicals with wide sources and low raw material costs. (2) The reaction does not require an additional solvent, making it a solvent-free reaction (neat reaction), which is highly atom-economical and environmentally friendly; (3) The reaction conditions are mild, requiring only light to initiate the reaction, without the need to add other catalysts or reagents, and the operation is simple; (4) The method for synthesizing 3-(trifluoromethyl)cyclobutane-1-one of the present invention provides a new technical route for the preparation of this type of compound and has significant prospects for industrial application.

[0016] It should be noted that the structures not described in this invention are not related to the design points and improvement directions of this invention, and are the same as or can be implemented using existing technologies, so they will not be elaborated here. Attached Figure Description

[0017] Figure 1 This is a schematic diagram of the reaction apparatus used in the embodiments of the present invention; Figure 2 This is a schematic diagram of the structure of the low-temperature photoreactor used in the embodiments of the present invention; Figure 3 The 3-(trifluoromethyl)cyclobutane-1-one in the embodiments of the present invention 19 F NMR spectrum; Figure 4 The 3-(trifluoromethyl)cyclobutane-1-one in the embodiments of the present invention 1 H NMR spectrum; Figure 5 The infrared spectrum of 3-(trifluoromethyl)cyclobutane-1-one is shown in the embodiment of the present invention. Detailed Implementation

[0018] The present invention is further illustrated below by way of examples, but these examples do not limit the invention to the scope of the embodiments described. Experimental methods not specifically described in the following examples are performed according to conventional methods and conditions, or as selected according to the product instructions. It should also be noted that the present invention requires the diketene cracking device and the low-temperature photoreactor device to be connected in series to ensure the smooth progress of the reaction, and the reaction system must be carried out under an inert nitrogen atmosphere.

[0019] The structure and purity of the compound were determined by nuclear magnetic resonance (NMR). 19 F NMR, 1 H NMR, 13 Confirmation was performed using C NMR, employing a Bruker AVANCE 300 NMR spectrometer, with deuterated chloroform (CDCl3) as the solvent.

[0020] Those skilled in the art will know that ketene (Formula II) gas can be prepared by high-temperature pyrolysis of diketene (Formula I), and this method is prior art in the field. For example, the literature *Science of Synthesis, 2006, Vol. 23, pp15-51* (Thieme Publishing, publication date 2006) discloses a method for pyrolysis of diketene at 550-650°C to produce ketene; see also the entry for "Cyclopropanone" by De Kimpe, N., in *Encyclopedia of Reagents for Organic Synthesis (EROS)*, John Wiley & Sons, Ltd., 2001 (publication date 2001). The ketene preparation methods described in the above literature can all be used in step (a) of this invention.

[0021] Preparation of (Formula II) Ketone:

[0022] Diketene is evaporated and passed into a cracking furnace heated to 550-650°C, where it is cracked to produce ketene gas, which is collected in a liquid nitrogen cold trap for subsequent reactions.

[0023] Preparation of (Formula IV) 3-(trifluoromethyl)cyclobutane-1-one: The ketene gas produced by the above cracking was reacted with 1,1,1-trifluoropropylene (Formula III) in a low-temperature photocatalytic reactor to carry out a [2+2] cycloaddition reaction to obtain the target product.

[0024] The following are preferred embodiments: Example 1

[0025] A 100 mL constant-pressure dropping funnel, a thermometer, and an adapter with a stopcock are installed on a 250 mL three-necked reaction flask equipped with a magnetic stirrer. These are connected via rubber tubing to a pyrolysis furnace, a liquid nitrogen cold trap, a low-temperature photocatalytic reactor, and 1,1,1-trifluoropropylene and nitrogen balloons. The reaction apparatus is as follows: Figure 1As shown. At the start of the reaction, the system was evacuated and purged with nitrogen three times. Then, 16.8 g (200 mmol) of diketene was added through a constant-pressure dropping funnel. The substrate was vaporized in a 150°C oil bath at 0.01 MPa (absolute pressure) and passed into a 580-600°C pyrolysis furnace. Ketene was collected using a liquid nitrogen cold trap. After pyrolysis, the reaction system was purged with nitrogen to restore the pressure. The pyrolysis furnace valve was closed, and the temperature of the cryogenic photoreactor was controlled at -20°C and the pressure at 0.01 MPa. The liquid nitrogen cold trap for collecting ketene was replaced with a dry ice-ethanol bath, and the temperature was slowly increased to allow ketene gas to enter the cryogenic photoreactor. The valve controlled the addition rate at approximately 2-4 mL / min (based on the gas volume at room temperature and pressure). Simultaneously, 1,1,1-trifluoropropylene gas was added to the cryogenic photoreactor at approximately 3-5 mL / min, for a total of 115 g (6.0 eq., relative to ketene). Irradiate with a 400 nm LED blue light lamp (10-25 W) for 5 hours until the reaction is complete. Purge with nitrogen, and absorb any unreacted gases with a 1 mol / L NaOH aqueous solution. The reaction product is a nearly colorless and transparent liquid, collected at the bottom of the low-temperature photocatalytic reactor. After purging with nitrogen, transfer the bottom liquid to a glass bottle, distill at atmospheric pressure, and collect the fraction to obtain 29.8 g of the target product 3-(trifluoromethyl)cyclobutane-1-one (based on diketene, 1 mol of diketene produces 2 mol of product, theoretical yield 55.2 g, yield 54.1%).

[0026] Product characterization: 19 F NMR (376 MHz, Chloroform-d) δ ppm -62.4 (m, 3F); 1 H NMR (400 MHz, Chloroform-d) δ 3.1 – 2.8 (m, 4H), 2.6 – 2.4 (m,1H); 13 C NMR (127 MHz, CDCl3) δ 211.5 (q, J = 30.0 Hz), 122.4 (q, J =284.5Hz), 54.6 (q, J = 9.8 Hz), 33.6 (q, J = 30.1 Hz).

[0027] Example 2

[0028] A 250 mL three-necked reaction flask equipped with a magnetic stirrer contains a 100 mL constant-pressure dropping funnel, a thermometer, and an adapter with a stopcock. A pyrolysis furnace, a liquid nitrogen cold trap, a low-temperature photocatalytic reactor, and 1,1,1-trifluoropropylene balloons and nitrogen balloons are connected via rubber tubing. The reaction apparatus is as follows: Figure 1 As shown. At the start of the reaction, the system was evacuated and purged with nitrogen three times. Then, 21.0 g (250 mmol) of diketene was added through a constant-pressure dropping funnel. The substrate was evaporated and vaporized in a 150°C oil bath at 0.01 MPa and passed into a 580-600°C pyrolysis furnace. Ketene was collected using a liquid nitrogen cold trap. After pyrolysis, the reaction system was purged with nitrogen to restore the pressure. The pyrolysis furnace valve was closed, and the temperature of the cryogenic photoreactor was controlled at -30°C and the pressure at 0.01 MPa. The liquid nitrogen cold trap for collecting ketene was replaced with a dry ice-ethanol bath, and the temperature was slowly increased to allow ketene gas to enter the cryogenic photoreactor. The valve controlled the addition rate at approximately 3-6 mL / min. Simultaneously, 1,1,1-trifluoropropylene gas was added to the cryogenic photoreactor at approximately 4-7 mL / min, for a total of 150 g (6.2 eq.). Irradiate with a 365 nm LED ultraviolet lamp (10-25 W) for 8 hours until the reaction is complete. Purge with nitrogen, and absorb any unreacted gases with a 1 mol / L NaOH aqueous solution. The reaction product is a nearly colorless and transparent liquid, collected at the bottom of the low-temperature photocatalytic reactor. After purging with nitrogen, transfer the bottom liquid to a glass bottle, distill at atmospheric pressure, and collect the fraction to obtain 33.8 g of the target product 3-(trifluoromethyl)cyclobutane-1-one (based on diketene, theoretical yield 69.0 g, yield 49.0%).

[0029] Example 3

[0030] A 250 mL three-necked reaction flask equipped with a magnetic stirrer contains a 100 mL constant-pressure dropping funnel, a thermometer, and an adapter with a stopcock. A pyrolysis furnace, a liquid nitrogen cold trap, a low-temperature photocatalytic reactor, and 1,1,1-trifluoropropylene balloons and nitrogen balloons are connected via rubber tubing. The reaction apparatus is as follows: Figure 1As shown. At the start of the reaction, the system was evacuated and purged with nitrogen three times. Then, 12.6 g (150 mmol) of diketene was added through a constant-pressure dropping funnel. The substrate was evaporated and vaporized in a 150°C oil bath at 0.01 MPa (absolute pressure) and passed into a 580-600°C pyrolysis furnace. Ketene was collected using a liquid nitrogen cold trap. After pyrolysis, the reaction system was purged with nitrogen to restore the pressure. The pyrolysis furnace valve was closed, and the temperature of the cryogenic photoreactor was controlled at -30°C and the pressure at 0.01 MPa. The liquid nitrogen cold trap for collecting ketene was replaced with a dry ice-ethanol bath, and the temperature was slowly increased to allow ketene gas to enter the cryogenic photoreactor. The valve controlled the addition rate at approximately 2-5 mL / min. Simultaneously, 1,1,1-trifluoropropylene gas was added to the cryogenic photoreactor at approximately 3-6 mL / min, for a total of 120 g (5.0 eq.). Irradiate with a 450 nm LED blue light lamp (10-25 W) for 8 hours until the reaction is complete. Purge with nitrogen, and absorb any unreacted gases with a 1 mol / L NaOH aqueous solution. The reaction product is a nearly colorless and transparent liquid, collected at the bottom of the low-temperature photocatalytic reactor. After purging with nitrogen, transfer the bottom liquid to a glass bottle, distill at atmospheric pressure, and collect the fraction to obtain 23.6 g of the target product 3-(trifluoromethyl)cyclobutane-1-one (based on diketene, theoretical yield 41.4 g, yield 57.0%).

[0031] Example 4

[0032] A 250 mL three-necked reaction flask equipped with a magnetic stirrer contains a 100 mL constant-pressure dropping funnel, a thermometer, and an adapter with a stopcock. A pyrolysis furnace, a liquid nitrogen cold trap, a low-temperature photocatalytic reactor, and 1,1,1-trifluoropropylene balloons and nitrogen balloons are connected via rubber tubing. The reaction apparatus is as follows: Figure 1As shown. At the start of the reaction, the system was evacuated and purged with nitrogen three times. Then, 10.5 g (125 mmol) of diketene was added through a constant-pressure dropping funnel. The substrate was evaporated and vaporized in a 150°C oil bath at 0.01 MPa (absolute pressure) and passed into a 580-600°C pyrolysis furnace. Ketene was collected using a liquid nitrogen cold trap. After pyrolysis, the reaction system was purged with nitrogen to restore the pressure. The pyrolysis furnace valve was closed, and the temperature of the cryogenic photoreactor was controlled at 0°C and the pressure at 0.01 MPa. The liquid nitrogen cold trap for collecting ketene was replaced with a dry ice-ethanol bath, and the temperature was slowly increased to allow ketene gas to enter the cryogenic photoreactor. The valve controlled the addition rate at approximately 1-3 mL / min. Simultaneously, 1,1,1-trifluoropropylene gas was added to the cryogenic photoreactor at approximately 2-4 mL / min, totaling approximately 85 g (4.0 eq.). Irradiate with a 500 nm LED green light (10-25 W) for 4 hours until the reaction is complete. Purge with nitrogen, and absorb any unreacted gases with a 1 mol / L NaOH aqueous solution. The reaction product is a nearly colorless, transparent liquid, collected at the bottom of the low-temperature photocatalytic reactor. After purging with nitrogen, transfer the bottom liquid to a glass bottle, distill at atmospheric pressure, and collect the fraction to obtain 21.4 g of the target product 3-(trifluoromethyl)cyclobutane-1-one (based on diketene, theoretical yield 34.5 g, yield 62.0%).

[0033] Example 5

[0034] A 250 mL three-necked reaction flask equipped with a magnetic stirrer contains a 100 mL constant-pressure dropping funnel, a thermometer, and an adapter with a stopcock. A pyrolysis furnace, a liquid nitrogen cold trap, a low-temperature photocatalytic reactor, and 1,1,1-trifluoropropylene balloons and nitrogen balloons are connected via rubber tubing. The reaction apparatus is as follows: Figure 1As shown. At the start of the reaction, the system was evacuated and purged with nitrogen three times. Then, 16.8 g (200 mmol) of diketene was added through a constant-pressure dropping funnel. The substrate was vaporized in a 150°C oil bath at 0.01 MPa (absolute pressure) and passed into a 580-600°C pyrolysis furnace. Ketene was collected using a liquid nitrogen cold trap. After pyrolysis, the reaction system was purged with nitrogen to restore the pressure. The pyrolysis furnace valve was closed, and the temperature of the cryogenic photoreactor was controlled at -30°C and the pressure at 0.01 MPa. The liquid nitrogen cold trap for collecting ketene was replaced with a dry ice-ethanol bath, and the temperature was slowly increased to allow ketene gas to enter the cryogenic photoreactor. The valve controlled the addition rate at approximately 1-3 mL / min. Simultaneously, 1,1,1-trifluoropropylene gas was added to the cryogenic photoreactor at approximately 2-6 mL / min, for a total of 134 g (7.0 eq.). Irradiate with a 550 nm LED green light (10-25 W) for 5 hours until the reaction is complete. Purge with nitrogen, and absorb any unreacted gases with a 1 mol / L NaOH aqueous solution. The reaction product is a nearly colorless, transparent liquid, collected at the bottom of the low-temperature photocatalytic reactor. After purging with nitrogen, transfer the bottom liquid to a glass bottle, distill at atmospheric pressure, and collect the fraction to obtain 32.7 g of the target product 3-(trifluoromethyl)cyclobutane-1-one (based on diketene, theoretical yield 55.2 g, yield 59.3%).

[0035] Detailed analysis of the product characterization spectra of this invention: 1. 19 F NMR spectrum analysis (see also) Figure 3 Numerical values: δ-62.40, A (m)-62.40, integral 1.00) 19 F NMR (376 MHz, Chloroform-d) δ -62.40 (m, 3F) The chemical shift δ -62.40 ppm is related to the saturated sp. 3 The characteristic chemical shift of the trifluoromethyl (-CF3) group directly bonded to the carbon atom matches the electronic environment of the CF3 group in 3-(trifluoromethyl)cyclobutane-1-one.

[0036] The peak shape is a multiplet (m), which is the splitting signal of the CF3 group and the single hydrogen atom on the adjacent methine (-CH-) and the two equivalent methylene (-CH2-) hydrogen atoms at the C2 and C4 positions on the cyclobutane ring. Since this is a chiral center, the splitting is more complex and is divided into multiplets.

[0037] The integral area is 1.00 (corresponding to 3 fluorine atoms), and there are no other fluorine signal peaks in the spectrum, proving that the product has no residual fluorine-containing byproducts.

[0038] 2. 1 H NMR spectrum analysis (see Figure 4, values: δ3.1-2.8 integral 4.00, δ2.6-2.4 integral 1.10, δ7.26 solvent peak) 1 H NMR (400 MHz, Chloroform-d) δ 3.1–2.8 (m, 4H), 2.6–2.4 (m, 1H) The multiplet (m) at δ 3.1–2.8 ppm, with an integral area of ​​4.00, corresponds to two equivalent methylene (-CH2-) hydrogen atoms at C2 and C4 positions on the cyclobutane ring. Due to conformational fluctuations of the cyclobutane ring, coupling with the adjacent methylene hydrogen at C3 position, and coupling with the CF3 fluorine, the peak shape exhibits multiplets, consistent with the characteristic 1H spectroscopy of 3-substituted cyclobutane-1-ones.

[0039] The multiplet (m) at δ 2.6–2.4 ppm, with an integral area of ​​1.10 (corresponding to one hydrogen atom within the experimental error range), corresponds to the methine (-CH-) hydrogen atom at the C3 position of the cyclobutane ring, directly bonded to the trifluoromethyl group. This hydrogen atom is simultaneously coupled by the two adjacent methylene hydrogens and the trifluoromethyl group, thus exhibiting a complex multiplet, similar to the one in Figure 3. 19 The coupling relationships of F NMR are completely consistent.

[0040] The single peak at δ 7.26 ppm is the solvent peak of deuterated chloroform (CDCl3), and there are no other obvious impurity peaks in the spectrum, which further proves the purity of the product.

[0041] 3. FT-IR spectral analysis (see Figure 5) Main characteristic absorption peaks (cm) -1 ) and attribution: wavenumber 1150 cm -1 -1280 cm -1 The strong absorption peak corresponds to the asymmetric stretching vibration of the CF bond in trifluoromethyl (-CF3), and is the most recognizable fingerprint peak group of organic compounds containing the CF3 group.

[0042] wavenumber 1719 cm -1 The extremely strong absorption peak corresponds to the stretching vibration of the carbonyl group (C=O) in cyclobutanone. Due to the increased ring strain, the carbonyl vibration frequency in cyclobutanone increases significantly. This is a characteristic fingerprint peak of cyclobutanone compounds, directly proving the presence of a ketone carbonyl group in the molecule.

[0043] wavenumber 2964 cm -1 The weak absorption peak corresponds to the stretching vibration of the CH bond on the cyclobutane ring.

[0044] Verification of the synthesis principle of this invention (based on) Figures 3-5 Spectral data): This invention prepares 3-(trifluoromethyl)cyclobutane-1-one via a [2+2] photocycloaddition reaction of ketene with 1,1,1-trifluoropropylene. 1 H NMR, 19 The F NMR and FT-IR characterization data corroborate each other, fully verifying the correctness of the reaction mechanism and the uniqueness of the product structure: 1. Verification of the characteristics of the [2+2] cycloaddition reaction: The core characteristics of the [2+2] photo-addition reaction are photoinitiation, no external catalyst, generation of a four-membered ring product, and complete preservation of the functional groups of the reactants. The technical solution and experimental results of this invention are completely consistent with the above characteristics: The reaction can be initiated simply by light irradiation with wavelengths of 250 nm to 650 nm, without the addition of any catalyst or initiator; The reaction product is a four-membered ring butanone structure, and no side reactions such as ring opening, polymerization or addition-elimination occurred; The carbonyl functional group in the ketene molecule is completely preserved during the reaction.

[0045] 2. Product structure verification (1) Verification of the four-membered ring structure 1 In the 1H NMR spectrum (Figure 4), the multiplet with an integrated area of ​​4.00 in the δ 3.1–2.8 ppm range corresponds to the two equivalent methylene hydrogen atoms at the C2 and C4 positions of the cyclobutane ring; the multiplet with an integrated area of ​​1.10 in the δ 2.6–2.4 ppm range corresponds to the methine hydrogen atom at the C3 position of the cyclobutane ring. The integration ratio of the two is approximately 4:1, which is consistent with the characteristic 1H NMR spectrum of 3-(trifluoromethyl)cyclobutane-1-one.

[0046] (2) Verification of carbonyl functional group FT-IR spectrum ( Figure 5 ) 1720 cm -1 The extremely strong absorption peak at that point is a characteristic peak of the stretching vibration of the ketone carbonyl group (C=O).

[0047] (3) Verification of the trifluoromethyl group 19 The multiplet at δ -62.4 ppm in the F NMR spectrum (Figure 3) is related to the saturated sp. 3The characteristic shift signal of trifluoromethyl (-CF3) with carbon atoms directly bonded is split into multiple peaks due to the presence of hydrogen on the ring and stereochemical chiral centers.

[0048] FT-IR spectrum (Figure 5) at 1150 cm⁻¹ -1 -1280 cm -1 The continuous strong absorption peaks at the CF3 position are characteristic peak groups of the asymmetric and symmetric stretching vibrations of the CF bond in trifluoromethyl groups, further confirming the presence of the CF3 group.

[0049] The experimental data above are completely consistent with the theoretical prediction of the [2+2] photocycloaddition reaction, which fully proves the feasibility of the synthesis method of the present invention and the correctness of the structure of the product 3-(trifluoromethyl)cyclobutane-1-one.

[0050] The above description is merely a preferred embodiment of the present invention and is not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for preparing 3-(trifluoromethyl)cyclobutane-1-one, characterized in that, Includes the following steps: (a) Diketene is decomposed at 550°C to 650°C under an inert atmosphere to generate ketene gas; (b) Under inert atmosphere and illumination conditions, at a temperature of -30°C to 0°C, the ketene gas obtained in step (a) undergoes a cycloaddition reaction with 1,1,1-trifluoropropylene gas to generate 3-(trifluoromethyl)cyclobutane-1-one; the wavelength of the light source is 365 nm to 550 nm.

2. The method for preparing 3-(trifluoromethyl)cyclobutane-1-one according to claim 1, characterized in that, The wavelength of the light source mentioned in step (b) is 365nm to 450nm.

3. The method for preparing 3-(trifluoromethyl)cyclobutane-1-one according to claim 1, characterized in that, The reaction temperature described in step (b) is -30℃ to -10℃.

4. The method for preparing 3-(trifluoromethyl)cyclobutane-1-one according to claim 1, characterized in that, The molar ratio of ketene gas to 1,1,1-trifluoropropylene gas in step (b) is 1:2 to 1:

10.

5. The method for preparing 3-(trifluoromethyl)cyclobutane-1-one according to claim 1, characterized in that, The reaction described in step (b) is carried out under conditions without the addition of external solvent.

6. The method for preparing 3-(trifluoromethyl)cyclobutane-1-one according to claim 1, characterized in that, Step (a) specifically involves: evaporating diketene, passing it into a pyrolysis zone heated to 550°C to 650°C for pyrolysis, and condensing and collecting the generated ketene gas in a cold trap.

7. The method for preparing 3-(trifluoromethyl)cyclobutane-1-one according to claim 1, characterized in that, After step (b) is completed, the unreacted gas is purged with an inert gas and the tail gas is absorbed with an alkaline solution.

8. The preparation method according to any one of claims 1-7, characterized in that, The preparation method further includes step (c): separating 3-(trifluoromethyl)cyclobutane-1-one from the reaction product of step (b) by distillation.

9. The method for preparing 3-(trifluoromethyl)cyclobutane-1-one according to claim 8, characterized in that, The distillation is atmospheric distillation.

10. The method for preparing 3-(trifluoromethyl)cyclobutane-1-one according to claim 6, characterized in that, The ketene gas mentioned in step (b) is introduced into the reaction system by slowly heating and vaporizing the ketene collected in step (a).

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