Preparation method of 2-chloromethyl-oxazole

Abstract

The invention discloses a preparation method of 2-chloromethyl-oxazole, which comprises the following steps: by taking 1H-1, 2, 3-triazole as a raw material, protecting 2-nitrogen by using trimethylhalogenosilane, performing 1-nitrogen acylation by using chloracetyl halide and simultaneously completing 2-nitrogen deprotection, vacuumizing in the reaction process and removing low-boiling-point byproducts, so that the reaction is performed in the forward direction, the materials are thoroughly reacted, and the 2-chloromethyl-oxazole is obtained. According to the method, the generation of an isomer of 2-nitrogen during acylation is avoided, the reaction selectivity of the raw materials is improved, the yield is higher, meanwhile, high-temperature rearrangement denitrification can be directly carried out without separating and purifying an intermediate compound, the reaction steps are simplified, the reaction efficiency is improved, and the method is suitable for industrial production. Conventional operation and conventional reagents are used, the operation is simple, industrial mass production is facilitated, and the production cost is reduced.

Description

Technical Field

[0001] The invention belongs to the field of synthesis of organic compounds, and specifically relates to a preparation method of 2-chloromethyl-oxazole. Background Art

[0002] Oxazole is a five-membered ring compound containing O and N atoms at the 1 and 3 positions. It has an odor similar to pyridine, is easily soluble in water, and has very stable chemical properties. Oxazole compounds are an important class of heterocyclic compounds with important biological activities. They are widely used in drug synthesis and polymer materials. For example, 2-aminooxazole has antifungal, antibacterial and antiviral effects, and polybenzoxazole is a high-temperature resistant polymer. Compounds with oxazole structures are currently a hot research target for the preparation of important bioactive drugs with antiviral, analgesic, antibacterial, anti-leukemia and anti-cancer activities. Patent WO 2011 / 035009 discloses an inhibitor of adenosine triphosphate cyclohydrolase (GCH-1) for the treatment of pain, in which multiple compound structures contain 2-methylene-oxazole building blocks, such as the specific structure. Figure 1 Patent WO 2017 / 093543 discloses an antibacterial drug for Gram-positive and Gram-negative bacterial infections, which also contains a compound containing a 2-methylene-oxazole building block, and the specific structure is as follows Figure 2 The 2-methylene-oxazole building blocks contained in the multiple compounds reported in the above patents can be obtained by coupling 2-halomethyl-oxazole with other intermediates. The efficient and economical synthesis of 2-chloromethyl-oxazole has important academic significance and economic value.

[0003] There are currently a variety of synthetic methods for the synthesis of 2-methylene-oxazole building blocks. The methods used in patents WO 2011 / 035009 and WO2017 / 093543 use oxazole as a raw material, synthesize an aldehyde group at the 2-position through a Grignard reaction, then use a boron reagent to reduce the aldehyde group to an alcohol, and finally halogenate the alcohol group, usually halogenate with a chlorine, to synthesize 2-chloromethyl-oxazole. The specific route is as follows: Figure 3 As shown; however, the price of the raw material oxazole is high, the reaction steps are many, the ultra-low temperature and anhydrous and oxygen-free Grignard reaction has high requirements for equipment and operators, the Grignard reagent and the boron reagent used for reduction are easy to catch fire, the operation is dangerous, and the safety risk is high. The method used in patent CN110698420A is to use 1H-1,2,3-triazole as raw material, diisopropylethylamine as acid binding agent, react with chloroacetyl chloride to generate substituted triazole, and finally high-temperature denitrification to obtain a crude product, which is then distilled to obtain a finished product. The specific route is as follows Figure 4As shown; this method has cheap raw materials, commonly used reagents, simple and easy-to-operate synthesis reactions, and relatively conventional reaction temperatures, and is an ideal preparation process. However, when 1H-1,2,3-triazole is acylated, there are isomers of 1-nitrogen and 2-nitrogen, and the 2-acylated product cannot undergo a denitrogenation reaction, that is, it cannot be converted from triazole to oxazole, thereby increasing the difficulty of product purification, resulting in a low product yield of the synthesis scheme, and it is not the best synthesis method. Therefore, developing a simple, efficient, economical and environmentally friendly method for preparing 2-chloromethyl-oxazole is a technical problem that needs to be solved urgently. Summary of the invention

[0004] The technical problem to be solved by the present invention is to provide a method for preparing 2-chloromethyl-oxazole which is simple in operation, high in yield, economical, environmentally friendly and suitable for large-scale industrial production, thereby overcoming the defects of the prior art.

[0005] The present invention uses 1H-1,2,3-triazole as a raw material, uses trimethyl halogen silane to protect the 2-nitrogen, then uses chloroacetyl halide to acylate the 1-nitrogen while completing the 2-nitrogen deprotection, vacuumizes during the reaction, removes low-boiling point byproducts, allows the reaction to proceed in the forward direction, and allows the materials to react completely, and finally uses a high-boiling point aprotic solvent for high-temperature reaction to rearrange and denitrify to obtain the product. The specific route is as follows: Figure 5 shown.

[0006] Specifically, the present invention provides a method for preparing 2-chloromethyl-oxazole, comprising the following steps: S1: Add compound A and solvent I into a reaction container, stir thoroughly, and lower the temperature of the mixed solution to 5-20°C, then add an acid binding agent, stir and react for 10 minutes to obtain a mixed solution A, and lower the temperature of the mixed solution A to 5-20°C, wherein the compound A is 1,2,3-triazole; S2: dissolving trimethylhalosilane in solvent I to prepare a mixed solution B of trimethylhalosilane-solvent I with a mass fraction of 30% to 50%, dripping the mixed solution B into the mixed solution A prepared in step S1, controlling the dropping temperature, and continuously stirring for 30 minutes to activate the solution reaction, controlling the temperature of the reaction solution, and keeping the temperature for a certain period of time to make the reaction sufficient, thereby obtaining a mixed solution C; S3: lowering the temperature of the mixed solution C obtained in step S2 to 20° C. to 30° C., filtering to obtain a filtrate and a filter cake, washing the filter cake with twice the weight of the solvent I in step S1, combining the washing liquid with the filtrate, and concentrating the combined liquid at a temperature of 45° C. to 60° C. to obtain a concentrated oily substance, and performing temperature-controlled reduced-pressure distillation on the concentrated oily substance to obtain compound B, wherein compound B is 2-(trimethylsilyl)-1,2,3-triazole; S4: dissolving chloroacetyl halide in a high-boiling-point aprotic solvent to prepare a mixed solution D of chloroacetyl halide-high-boiling-point aprotic solvent with a mass fraction of 25% to 40%, adding the compound B obtained in step S3 to a reaction container, and then adding a high-boiling-point aprotic solvent, stirring for 10 minutes, controlling the temperature of the mixed solution to 5°C to 25°C, dripping the mixed solution D, controlling the dropping temperature, and continuously stirring for 30 minutes to activate the solution reaction, controlling the temperature of the reaction solution, and keeping the temperature for a certain period of time to allow the reaction to be sufficient, thereby obtaining a mixed solution E; S5: The mixed solution E obtained in step S4 is subjected to a temperature-controlled vacuum distillation until no fraction is distilled out, and after the low-boiling-point trimethylhalosilane is removed, the vacuum distillation is stopped to obtain a mixed solution F of compound C and a high-boiling-point aprotic solvent. After being fully stirred, the mixed solution F is subjected to a high-temperature denitrogenation rearrangement reaction. A large number of bubbles will be generated during the reaction. After basically no bubbles are released, the solution is fully stirred, and the solution after the reaction is subjected to a second temperature-controlled vacuum distillation to finally obtain compound D, wherein compound D is 2-chloromethyl-oxazole.

[0007] Preferably, in step S1, the solvent I is selected from one of chloroform, carbon tetrachloride, 1,2-dichloroethane, tetrahydrofuran, methyltetrahydrofuran, isopropyl ether, and methyl tert-butyl ether; more preferably, the solvent I is 1,2-dichloroethane.

[0008] Preferably, in step S1, the acid binding agent is selected from one of triethylamine, pyridine, potassium carbonate and sodium carbonate; more preferably, the acid binding agent is triethylamine.

[0009] Preferably, calculated by molar ratio, in step S1, the acid binding agent: compound A = 1.1 to 1.4:1; more preferably, the acid binding agent: compound A = 1.25:1.

[0010] Preferably, in step S2, the trimethylhalosilane is selected from one of trimethylchlorosilane, trimethylbromosilane and trimethyliodosilane; more preferably, the trimethylhalosilane is trimethylchlorosilane; Preferably, calculated by molar ratio, in step S2, the ratio of trimethylhalosilane to compound A is 1 to 1.25:1; more preferably, the ratio of trimethylhalosilane to compound A is 1.15:1; Preferably, the dropping temperature in step S2 is 5 to 20°C; more preferably, the dropping temperature is 5 to 10°C.

[0011] Preferably, in step S2, the temperature of the reaction solution is 45°C to 60°C, and the reaction time is 4 to 8 hours; more preferably, the temperature of the reaction solution is 50°C to 55°C, and the reaction time is 5 hours.

[0012] Preferably, the temperature of the temperature-controlled reduced-pressure distillation in step S3 is 90° C. to 95° C., and the pressure is -0.09 MPa to -0.095 MPa.

[0013] Preferably, in step S4, the chloroacetyl halide is selected from one of chloroacetyl chloride, chloroacetyl bromide, chloroacetyl fluoride and chloroacetyl iodine; more preferably, the chloroacetyl halide is chloroacetyl chloride.

[0014] Preferably, the high boiling point aprotic solvent in step S4 is selected from one of N,N-dimethylformamide, N,N-diethylformamide, dimethyl sulfoxide and sulfolane; more preferably, the high boiling point aprotic solvent is sulfolane.

[0015] Preferably, calculated by molar ratio, in step S4, chloroacetyl halide: compound B = 1 to 1.2: 1; more preferably, chloroacetyl halide: compound B = 1.1: 1.

[0016] Preferably, the dropping temperature in step S4 is 5 to 25°C; more preferably, the dropping temperature is 10 to 15°C.

[0017] Preferably, in step S4, the temperature of the reaction solution is 30°C to 50°C, and the reaction time is 22 to 28 hours; more preferably, the temperature of the reaction solution is 38°C to 42°C, and the reaction time is 24 hours.

[0018] Preferably, the temperature of the primary temperature-controlled reduced-pressure distillation in step S5 is 30° C. to 60° C., and the pressure is -0.09 MPa to -0.095 MPa.

[0019] Preferably, the temperature of the high-temperature denitrification rearrangement reaction in step S5 is 140°C to 180°C, and the reaction time is 1 to 4 hours; more preferably, the temperature of the high-temperature denitrification rearrangement reaction is 150°C to 160°C, and the reaction time is 2 hours.

[0020] Preferably, the temperature of the secondary temperature-controlled reduced-pressure distillation in step S5 is 140° C. to 180° C., and the pressure is -0.09 MPa to -0.095 MPa. Compared with the prior art, the present invention has the following beneficial effects: (1) The present invention avoids the formation of 2-nitrogen isomers during acylation, thereby improving the reaction selectivity of the raw materials and increasing the yield. The comprehensive weight yield can reach more than 116.5%; (2) By taking advantage of the difference in boiling points between the product and the by-product, the low-boiling-point by-product is removed by negative pressure, so that the material reacts completely. The next step of high-temperature rearrangement and denitrification reaction can be carried out directly without separation and purification of the intermediate compounds, thus simplifying the reaction steps and improving the reaction efficiency. (3) The present invention uses conventional operations and conventional reagents, is simple to operate, is conducive to large-scale industrial production, reduces production costs, conforms to the development concept of environmental friendliness and resource conservation, promotes the technological innovation of the preparation process of 2-chloromethyl-oxazole and its derivatives, and can provide stable and reliable raw material support for the preparation of related drugs containing oxazole building blocks, and also provides ideas for the synthesis of oxazole derivatives from triazole. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0022] Figure 1 The compound structure containing 2-methylene-oxazole building block in patent WO 2011 / 035009; Figure 2 The compound structure containing 2-methylene-oxazole building block in patent WO 2017 / 093543; Figure 3 A route for synthesizing 2-methylene-oxazole building blocks reported in patents WO 2011 / 035009 and WO 2017 / 093543; Figure 4 A route map for synthesizing 2-methylene-oxazole building blocks reported in patent CN110698420A; Figure 5 The synthetic route for preparing 2-methylene-oxazole of the present invention is as follows; Figure 6 This is the NMR spectrum of 2-methylene-oxazole. DETAILED DESCRIPTION

[0023] The following examples are used to illustrate the present invention, but are not intended to limit the scope of the present invention. Without departing from the spirit and substance of the present invention, modifications or substitutions made to the method, steps or conditions of the present invention are within the scope of the present invention. Unless otherwise specified, the chemical reagents used in the examples are conventional commercial reagents, and the technical means used in the examples are conventional means well known to those skilled in the art.

[0024] The term "weight yield" is defined as: weight yield = (target product weight / reactant weight) × 100%, wherein: the reactant weight is the weight of the main raw material used for the reaction. Example

[0025] Add 20g 1,2,3-triazole and 160g chloroform to the reaction container, stir well, lower the temperature of the mixed solution to 10°C, add 25.2g pyridine, stir and react for 10 minutes to obtain a mixed solution A, and adjust the temperature of the mixed solution A to 10°C; dissolve 70g trimethylsilyl iodide in 70g chloroform to prepare a mixed solution B, and then drop the mixed solution B into the mixed solution A, and control the dropping temperature to 10°C. After the dropwise addition, continue stirring for 30min, control the temperature of the reaction solution within the range of 45°C to 48°C, and keep the temperature for reaction for 8h. After the reaction is sufficient, obtain a mixed solution C, lower the temperature of the mixed solution C to 25°C, filter, obtain a filtrate and a filter cake, and use 40g The mixture was washed with chloroform, and the washing liquid was combined with the filtrate, and concentrated at 50°C to obtain an oily substance, which was subjected to temperature-controlled reduced-pressure distillation at a temperature range of 90°C to 95°C and a pressure range of -0.09Mpa to -0.095MPa, until no fraction was distilled out, to obtain 2-(trimethylsilyl)-1,2,3-triazole, with a weight of 34.4 g, and a calculated weight yield of 172%.

[0026] 27.6 g of chloroacetyl bromide was dissolved in 75 g of N,N-dimethylformamide to prepare a mixed solution D. 25 g of 2-(trimethylsilyl)-1,2,3-triazole and 125 g of N,N-dimethylformamide were added to a reaction container and stirred for 10 min. The temperature of the mixed solution was controlled at 10°C. The mixed solution D was added dropwise at a temperature of 10°C and stirred continuously for 30 min. The temperature of the reaction solution was controlled within the range of 30°C to 35°C. The mixture was kept warm for 28 h. After the reaction was sufficient, a mixed solution E was obtained. The mixed solution E was subjected to temperature-controlled vacuum distillation at a temperature range of 30°C to 60°C and a pressure range of -0.09 MPa to -0.095 MPa. The mixture was distilled until no fraction was distilled out to remove trimethylbromosilane with a low boiling point. The vacuum distillation was stopped. A mixed solution F of 1-chloroacetyl-1,2,3-triazole and N,N-dimethylformamide is obtained. After being fully stirred, the mixed solution F is subjected to a high-temperature denitrogenation rearrangement reaction. The temperature is controlled in the range of 140°C to 150°C. The reaction time is 4 hours. A large number of bubbles will be generated during the reaction. After almost no bubbles are released, the solution is fully stirred. The solution after the reaction is subjected to temperature-controlled reduced-pressure distillation. The temperature range is 140°C to 180°C. The pressure range is -0.09Mpa to -0.095MPa. Finally, 2-chloromethyl-oxazole is obtained. The weighed mass is 17g, and the calculated weight yield can reach 68%.

[0027] The product of the single-step weight yields of the two steps was calculated to obtain a comprehensive weight yield of 116.96%.

[0028] The final product was subjected to nuclear magnetic resonance detection, and the peak information of nuclear magnetic resonance detection was 1H-NMR {400 MHz, CDCl3(TMS), δ(ppm)}: 7.68(s, 1H),7.14 (s, 1H),4.63 (d, 2H), indicating that the product was indeed 2-chloromethyl-oxazole. Example

[0029] Add 28g 1,2,3-triazole and 210g 1,2-dichloroethane to the reaction container, stir well, lower the temperature of the mixed solution to 10°C, add 51.25g triethylamine, stir and react for 10 minutes to obtain a mixed solution A, and adjust the temperature of the mixed solution A to 10°C; dissolve 50.68g trimethylsilyl iodide in 100g 1,2-dichloroethane to prepare a mixed solution B, and then drip the mixed solution B into the mixed solution A, and control the dripping temperature to 10°C. After the dripping is completed, continue stirring for 30min, control the temperature of the reaction solution to 50-55°C, and keep the temperature for reaction for 5h. After the reaction is sufficient, obtain a mixed solution C, lower the temperature of the mixed solution C to 25°C, filter, obtain a filtrate and a filter cake, and use 56g The mixture was washed with 1,2-dichloroethane, and the washing liquid and the filtrate were combined and concentrated at 50°C to obtain an oily substance. The oily substance was subjected to temperature-controlled reduced-pressure distillation at a temperature range of 90°C to 95°C and a pressure range of -0.09Mpa to -0.095MPa, and distilled until no fraction was distilled out to obtain 2-(trimethylsilyl)-1,2,3-triazole. The weight obtained was 51.8 g, and the calculated weight yield could reach 185%.

[0030] 15.83g of chloroacetyl chloride was dissolved in 38g of sulfolane to prepare a mixed solution D. 18g of 2-(trimethylsilyl)-1,2,3-triazole and 72g of sulfolane were added to a reaction container and stirred for 10min. The temperature of the mixed solution was controlled at 10°C. The mixed solution D was added dropwise at a temperature of 10°C and stirred for 30min. The temperature of the reaction solution was controlled within the range of 38°C to 42°C. The mixture was kept warm for 24h. After the reaction was sufficient, a mixed solution E was obtained. The mixed solution E was subjected to temperature-controlled vacuum distillation at a temperature range of 38°C to 60°C and a pressure range of -0.09Mpa to -0.095MPa. The mixture was distilled until no fraction was distilled out to remove trimethylchlorosilane with a low boiling point. The vacuum distillation was stopped. A mixed solution F of 1-chloroacetyl-1,2,3-triazole and cyclopentane sulfone was obtained. After being fully stirred, the mixed solution F was subjected to a high-temperature denitrogenation rearrangement reaction. The temperature was controlled within the range of 150°C to 160°C. The reaction time was 2 hours. A large number of bubbles were generated during the reaction. After almost no bubbles were released, the solution was fully stirred. The solution after the reaction was subjected to temperature-controlled reduced-pressure distillation. The temperature range was 150°C to 180°C. The pressure value range was -0.09Mpa to -0.095MPa. Finally, 2-chloromethyl-oxazole was obtained. The weight obtained by weighing was 13.5g. The calculated weight yield could reach 75%.

[0031] The product of the single-step weight yields of the two steps was calculated to obtain a comprehensive weight yield of 138.75%.

[0032] The final product was subjected to nuclear magnetic resonance detection, and the peak information of nuclear magnetic resonance detection was 1H-NMR {400 MHz, CDCl3(TMS), δ(ppm)}: 7.68(s, 1H),7.14 (s, 1H),4.63 (d, 2H), indicating that the product was indeed 2-chloromethyl-oxazole. Example

[0033] 26 g of 1,2,3-triazole and 221 g of tetrahydrofuran were added to the reaction container and stirred thoroughly. The temperature of the mixed solution was lowered to 10°C. 72.8 g of potassium carbonate was added and stirred for 10 minutes to obtain a mixed solution A. The temperature of the mixed solution A was adjusted to 10°C. 67.6 g of trimethylsilyl bromide was dissolved in 83.2 g of Tetrahydrofuran is added to prepare a mixed solution B, and then the mixed solution B is dripped into the mixed solution A, and the dripping temperature is controlled at 10°C. After the dripping is completed, stirring is continued for 30 minutes, and the temperature of the reaction solution is controlled within the range of 55°C to 60°C. The reaction is kept warm for 4 hours. After the reaction is sufficient, a mixed solution C is obtained. The temperature of the mixed solution C is reduced to 25°C, and filtered to obtain a filtrate and a filter cake. The filter cake is washed with 52g of tetrahydrofuran, and the washing liquid is combined with the filtrate, and concentrated at 50°C to obtain an oily substance. The oily substance is subjected to temperature-controlled reduced-pressure distillation in the temperature range of 90°C to 95°C and the pressure range of -0.09Mpa to -0.095MPa, and distilled until no fraction is distilled out to obtain 2-(trimethylsilyl)-1,2,3-triazole. The weighed mass is 46 g, and the calculated weight yield can reach 176.9%.

[0034] 32.5 g of chloroacetyl iodide was dissolved in 55 g of dimethyl sulfoxide to prepare a mixed solution D. 22 g of 2-(trimethylsilyl)-1,2,3-triazole and 165 g of dimethyl sulfoxide were added to a reaction container and stirred for 10 min. The temperature of the mixed solution was controlled at 10°C. The mixed solution D was added dropwise at a temperature of 10°C and stirred for 30 min. The temperature of the reaction solution was controlled within the range of 45°C to 50°C. The mixture was kept warm for 22 h. After the reaction was sufficient, a mixed solution E was obtained. The mixed solution E was subjected to temperature-controlled vacuum distillation at a temperature range of 45°C to 60°C and a pressure range of -0.09 MPa to -0.095 MPa. The mixture was distilled until no fraction was distilled out to remove trimethyl iodosilane with a low boiling point. The vacuum distillation was stopped. A mixed solution F of 1-chloroacetyl-1,2,3-triazole and dimethyl sulfoxide is obtained. After being fully stirred, the mixed solution F is subjected to a high-temperature denitrogenation rearrangement reaction. The temperature is controlled within the range of 170°C to 180°C. The reaction time is 1h. A large number of bubbles are generated during the reaction. After almost no bubbles are released, the solution is fully stirred. The solution after the reaction is subjected to temperature-controlled reduced-pressure distillation. The temperature range is 170°C to 180°C. The pressure range is -0.09Mpa to -0.095MPa. Finally, 2-chloromethyl-oxazole is obtained. The weight obtained by weighing is 14.5g. The calculated weight yield can reach 65.9%.

[0035] The single-step weight yields of the two steps were multiplied to obtain a comprehensive weight yield of 116.58%.

[0036] The final product was subjected to nuclear magnetic resonance detection, and the peak information of nuclear magnetic resonance detection was 1H-NMR {400 MHz, CDCl3(TMS), δ(ppm)}: 7.68(s, 1H),7.14 (s, 1H),4.63 (d, 2H), indicating that the product was indeed 2-chloromethyl-oxazole. Although the present invention has been described in detail above with general descriptions and specific embodiments, it is obvious to those skilled in the art that some modifications or improvements may be made thereto based on the present invention. Therefore, these modifications or improvements made without departing from the spirit of the present invention all fall within the scope of protection claimed by the present invention.

Claims

1. A method for preparing 2-chloromethyl-oxazole, characterized in that: The following steps are involved: S1: Add compound A and solvent I into a reaction container, stir thoroughly, and lower the temperature of the mixed solution to 5-20°C, then add an acid binding agent, stir and react for 10 minutes to obtain a mixed solution A, and lower the temperature of the mixed solution A to 5-20°C, wherein the compound A is 1,2,3-triazole; S2: dissolving trimethylhalosilane in solvent I to prepare a mixed solution B of trimethylhalosilane-solvent I with a mass fraction of 30% to 50%, dripping the mixed solution B into the mixed solution A prepared in step S1, controlling the dropping temperature, and continuously stirring for 30 minutes to activate the solution reaction, controlling the temperature of the reaction solution, and keeping the temperature for a certain period of time to make the reaction sufficient, thereby obtaining a mixed solution C; S3: lowering the temperature of the mixed solution C obtained in step S2 to 20° C. to 30° C., filtering to obtain a filtrate and a filter cake, washing the filter cake with twice the weight of the solvent I in step S1, combining the washing liquid with the filtrate, and concentrating the combined liquid at a temperature of 45° C. to 60° C. to obtain a concentrated oily substance, and performing temperature-controlled reduced-pressure distillation on the concentrated oily substance to obtain compound B, wherein compound B is 2-(trimethylsilyl)-1,2,3-triazole; S4: dissolving chloroacetyl halide in a high-boiling-point aprotic solvent to prepare a mixed solution D of chloroacetyl halide-high-boiling-point aprotic solvent with a mass fraction of 25% to 40%, adding the compound B obtained in step S3 to a reaction container, and then adding a high-boiling-point aprotic solvent, stirring for 10 minutes, controlling the temperature of the mixed solution to 5°C to 25°C, dripping the mixed solution D, controlling the dropping temperature, and continuously stirring for 30 minutes to activate the solution reaction, controlling the temperature of the reaction solution, and keeping the temperature for a certain period of time to allow the reaction to be sufficient, thereby obtaining a mixed solution E; S5: The mixed solution E obtained in step S4 is subjected to a temperature-controlled vacuum distillation until no fraction is distilled out, and after the low-boiling-point trimethylhalosilane is removed, the vacuum distillation is stopped to obtain a mixed solution F of compound C and a high-boiling-point aprotic solvent. After being fully stirred, the mixed solution F is subjected to a high-temperature denitrogenation rearrangement reaction. A large number of bubbles will be generated during the reaction. After basically no bubbles are released, the solution is fully stirred, and the solution after the reaction is subjected to a second temperature-controlled vacuum distillation to finally obtain compound D, wherein compound D is 2-chloromethyl-oxazole.

2. The method for preparing 2-chloromethyl-oxazole according to claim 1, characterized in that: In the step S1, the solvent I is selected from one of chloroform, carbon tetrachloride, 1,2-dichloroethane, tetrahydrofuran, methyltetrahydrofuran, isopropyl ether, and methyl tert-butyl ether; the acid binding agent is selected from one of triethylamine, pyridine, potassium carbonate, and sodium carbonate; and the trimethylhalosilane in the step S2 is selected from one of trimethylchlorosilane, trimethylbromosilane, and trimethyliodosilane.

3. The method for preparing 2-chloromethyl-oxazole according to claim 1, characterized in that: Calculated by molar ratio, in step S1, the acid binding agent: compound A = 1.1 to 1.4: 1, and in step S2, the trimethylhalosilane: compound A = 1 to 1.25:

1.

4. The method for preparing 2-chloromethyl-oxazole according to claim 1, characterized in that: In step S2, the dropping temperature is 5-20° C., the temperature of the reaction solution is 45-60° C., and the reaction time is 4-8 hours.

5. The method for preparing 2-chloromethyl-oxazole according to claim 1, characterized in that: The temperature of the temperature-controlled reduced-pressure distillation in step S3 is 90° C. to 95° C., and the pressure is -0.09 MPa to -0.095 MPa.

6. The method for preparing 2-chloromethyl-oxazole according to claim 1, characterized in that: In step S4, the chloroacetyl halide is selected from one of chloroacetyl chloride, chloroacetyl bromide, chloroacetyl fluoride and chloroacetyl iodide, and the high boiling point aprotic solvent is selected from one of N,N-dimethylformamide, N,N-diethylformamide, dimethyl sulfoxide and sulfolane.

7. The method for preparing 2-chloromethyl-oxazole according to claim 1, characterized in that: Calculated by molar ratio, in step S4, chloroacetyl halide: compound B = 1~1.2:

1.

8. The method for preparing 2-chloromethyl-oxazole according to claim 1, characterized in that: In step S4, the dropping temperature is 5°C to 25°C, the temperature of the reaction solution is 30°C to 50°C, and the reaction time is 22 to 28 hours.

9. The method for preparing 2-chloromethyl-oxazole according to claim 1, characterized in that: The temperature of the first temperature-controlled vacuum distillation in step S5 is 30°C~60°C, and the pressure value is -0.09MPa~-0.095MPa. The temperature of the high-temperature denitrogenation rearrangement reaction is 140°C~180°C, and the reaction time is 1~4h. The temperature of the second temperature-controlled vacuum distillation is 140°C~180°C, and the pressure value is -0.09MPa~-0.095MPa.

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