Synthesis method of 2-dimethylamino-2-oxo-1, 3, 2-dioxaphospholane

Abstract

The invention discloses a synthesis method of 2-dimethylamino-2-oxo-1, 3, 2-dioxaphospholane, which comprises the following operation steps: S10, respectively adding phosphorus oxyfluoride and a first solvent into a reaction device, dropwise adding 1, 2-bis (trimethylsiloxy) ethane into the reaction device to carry out primary reaction, then heating to carry out first heat preservation reaction, and carrying out second heat preservation reaction; intermediate reaction liquid is obtained; s20, dropwise adding a dimethylamine solution into the reaction device, and carrying out a second heat preservation reaction to obtain a reaction solution; s30, filtering to obtain filtrate, and performing rotary evaporation on the filtrate to obtain an evaporated substrate; adding a second solvent into the evaporated substrate for dissolving, and filtering to remove residual ammonium salt, so as to obtain a 2-dimethylamino-2-oxo-1, 3, 2-dioxaphospholane solution; the method has the advantages of high production efficiency, low energy consumption, high reaction selectivity and few side reactions, and is very suitable for being used as a process route for batch production of the 2-dimethylamino-2-oxo-1, 3, 2-dioxaphospholane.

Description

Technical Field

[0001] The present invention belongs to the field of synthesis of phospholane compounds, and particularly relates to a method for synthesizing 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane. Background Art

[0002] With the continuous progress of technology, the demand for new functional compounds is increasing day by day. Due to their unique structures and properties, phospholane compounds exhibit great application potential in multiple fields.

[0003] Phospholane compounds are often associated with biological activities. Some compounds with similar structures have been proven to have antibacterial, antiviral, antitumor and other activities, providing new directions for drug research and development. The special structure of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane may bring new opportunities for the design and development of new drugs, and is expected to become a drug molecular skeleton with unique efficacy. At the same time, it may also play an important role in the application of lithium batteries, endowing the batteries with excellent flame retardancy, thermal stability and other properties. In addition, as a special organic intermediate, it can participate in a variety of chemical reactions, providing a new way for the synthesis of complex organic molecules. Its unique reaction activity and selectivity may inspire the innovation of organic synthesis methods.

[0004] At present, it is difficult to find relevant reference documents on the synthesis method of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane, and no industrial method for realizing batch synthesis has been found.

[0005] In order to realize the industrial application of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane, the applicant hopes to seek technical solutions to realize the synthesis of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane. Summary of the Invention

[0006] In view of this, the purpose of the present invention is to provide a method for synthesizing 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane, which not only has high production efficiency, low energy consumption, but also has high reaction selectivity and few side reactions, and is very suitable for use as a process route for batch production of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane.

[0007] The technical solution adopted by the present invention is as follows: A method for synthesizing 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane, comprising the following operating steps: S10. Add phosphorus oxychloride and the first solvent into the reaction device respectively, dropwise add 1,2-bis(trimethylsilyloxy)ethane into the reaction device for a preliminary reaction, and then raise the temperature for the first heat preservation reaction to obtain an intermediate reaction solution. S20. Dropwise add a dimethylamine solution into the reaction device of the intermediate reaction solution obtained in the above step S10 for the second heat preservation reaction to obtain a 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane reaction solution. S30. Filter the 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane reaction solution obtained in the above step S20 to obtain a filtrate, and then perform rotary evaporation on the filtrate to obtain an evaporated substrate; add a second solvent to the evaporated substrate for dissolution, and filter to remove residual ammonium salts to obtain a 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane solution.

[0008] Preferably, in the step S10, the dropping time of the 1,2-bis(trimethylsilyloxy)ethane is 2 - 6 hours, preferably 4 - 5 hours; when dropping the 1,2-bis(trimethylsilyloxy)ethane, the temperature of the reaction device is controlled at -10 to 20 °C, more preferably 10 to 20 °C; the temperature of the first heat preservation reaction is set at 20 - 100 °C, more preferably 30 - 45 °C; the reaction time of the heat preservation reaction is 5 - 10 hours, more preferably 8 - 10 hours.

[0009] Preferably, in the step S10, the molar feed ratio of the phosphorus oxychloride to the 1,2-bis(trimethylsilyloxy)ethane is 1:0.9 - 1.2, more preferably 1:0.95 - 1.

[0010] Preferably, in the step S10, the first solvent is any one or a mixture of several of polar solvents or non-polar solvents; among them, the polar solvents are any one or a mixture of several of acetone, methyl ethyl ketone, ethyl acetate, propyl acetate, dichloromethane, chloroform, 1,2-dichloroethane, dimethyl sulfoxide, N,N-dimethylformamide, tetrahydrofuran and 1,4-dioxane; the non-polar solvents are any one or a mixture of several of benzene, toluene, xylene, cyclohexane, n-hexane and n-heptane; the dosage of the first solvent is 5 - 20 times the weight of the 1,2-bis(trimethylsilyloxy)ethane.

[0011] Preferably, in the step S20, when dropping the dimethylamine solution, the temperature of the reaction device is controlled at -10 to 10 °C, more preferably -10 to -5 °C; the temperature of the second heat preservation reaction is set at 0 - 30 °C, more preferably 20 - 30 °C; the reaction time of the second heat preservation reaction is 3 - 10 hours, more preferably 4 - 8 hours.

[0012] Preferably, in the step S20, the dimethylamine solution is any one or a mixture of several of dimethylamine-tetrahydrofuran solution, dimethylamine-dioxane solution, and dimethylamine-methanol solution; the concentration of the dimethylamine solution is 1.5-2.5 mol / L.

[0013] Preferably, in the step S20, the molar ratio of dimethylamine to phosphorus oxychloride in the dimethylamine solution is 0.9-2.5:1, more preferably 1.5-2:1.

[0014] Preferably, in the step S30, the second solvent is any one or a mixture of several of polar solvents or non-polar solvents; wherein, the polar solvents are any one or a mixture of several of methanol, ethanol, n-propanol, isopropanol, acetone, butanone, ethyl acetate, propyl acetate, dichloromethane, chloroform, 1,2-dichloroethane, dimethyl sulfoxide, N,N-dimethylformamide, ether, tetrahydrofuran, and 1,4-dioxane; the non-polar solvents are any one or a mixture of several of benzene, toluene, xylene, cyclohexane, n-hexane, and n-heptane.

[0015] Preferably, in the step S30, the addition amount of the second solvent is 2-10 times the weight of the substrate after evaporation.

[0016] Preferably, after the step S30, the following step S40 is further included: The 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane solution obtained in the above step S30 is subjected to rotary evaporation; then the rotary evaporation substrate is stirred and crystallized under low temperature conditions, and the 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane product is obtained after filtration.

[0017] This application adopts the following synthesis route: ; First, phosphorus oxytri fluoride reacts with 1,2-bis(trimethylsilyloxy)ethane to obtain the reaction intermediate 2-fluoro-2-oxo-1,3,2-dioxaphospholane (i.e., STEP1, corresponding to step S10 to obtain an intermediate reaction solution). The reaction rate is fast and the selectivity is high. Then, it directly reacts with dimethylamine to synthesize a 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane reaction solution. After filtration, rotary evaporation, solvent dissolution and extraction, and filtration to remove residual ammonium salts, a 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane solution is obtained (the pure product of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane can be obtained after removing the solvent). The reaction route proposed in this application not only has high production efficiency and low energy consumption, but also has high reaction selectivity, few side reactions, and does not require rectification and purification of the reaction intermediate, and is very suitable for use as a process route for batch production of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane. Description of the Drawings

[0018] Figure 1 It is a characterization diagram of the 1H NMR spectrum of the white crystal compound of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane obtained in Example 1 of the present invention; Figure 2 It is a characterization diagram of the 13C NMR spectrum of the white crystal compound of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane obtained in Example 1 of the present invention; Figure 3 It is a characterization diagram of the 31P NMR spectrum of the white crystal compound of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane obtained in Example 1 of the present invention. Detailed Description of the Invention

[0019] This embodiment provides a method for synthesizing 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane, including the following operating steps: S10. Add phosphorus oxychloride and the first solvent into the reaction device respectively, dropwise add 1,2-bis(trimethylsilyloxy)ethane into the reaction device for preliminary reaction, and then raise the temperature for the first heat preservation reaction to obtain an intermediate reaction solution. Preferably, in this step S10, the dropping time of 1,2-bis(trimethylsilyloxy)ethane is 2 - 6 hours, preferably 4 - 5 hours; when dropping 1,2-bis(trimethylsilyloxy)ethane, the temperature of the reaction device is controlled at -10 to 20°C, more preferably 10 to 20°C; the temperature of the first heat preservation reaction is set at 20 - 100°C, more preferably 30 - 45°C; the reaction time of the heat preservation reaction is 5 - 10 hours, more preferably 8 - 10 hours; the molar ratio of phosphorus oxychloride to 1,2-bis(trimethylsilyloxy)ethane is 1:0.9 - 1.2, more preferably 1:0.95 - 1, and most preferably 1:0.98; the first solvent is any one or a mixture of several of polar solvents or non-polar solvents; among them, the polar solvents are any one or a mixture of several of acetone, butanone, ethyl acetate, propyl acetate, dichloromethane, chloroform, 1,2-dichloroethane, dimethyl sulfoxide, N,N-dimethylformamide, tetrahydrofuran, and 1,4-dioxane; the non-polar solvents are any one or a mixture of several of benzene, toluene, xylene, cyclohexane, n-hexane, and n-heptane; the dosage of the first solvent is 5 - 20 times the weight of 1,2-bis(trimethylsilyloxy)ethane; it should also be noted that when this application is implemented, phosphorus oxychloride can be introduced into the reaction device in the form of a gas, or added to the reaction device in the form of a prepared phosphorus oxychloride solution. Among them, the solvent of the phosphorus oxychloride solution can be any one or a mixture of several of dichloromethane, tetrahydrofuran, and dimethyl carbonate, or other suitable solvents, and this embodiment does not make special restrictions on this; S20. Dropwise add dimethylamine solution into the reaction device of the intermediate reaction solution obtained in the above step S10 for the second heat preservation reaction to obtain a 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane reaction solution. Preferably, in this step S20, when dropping the dimethylamine solution, the temperature of the reaction device is controlled at -10 to 10°C, more preferably -10 to -5°C; the temperature of the second heat preservation reaction is set at 0 - 30°C, more preferably 20 - 30°C; the reaction time of the second heat preservation reaction is 3 - 10 hours, more preferably 4 - 8 hours; the dimethylamine solution is any one or a mixture of several of dimethylamine-tetrahydrofuran solution, dimethylamine-dioxane solution, and dimethylamine-methanol solution; the concentration of the dimethylamine solution is 1.5 - 2.5 mol / L; the molar ratio of dimethylamine to phosphorus oxychloride in the dimethylamine solution is 0.9 - 2.5:1, more preferably 1.5 - 2:1; S30. Filter the reaction solution of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane obtained in the above step S20 to obtain a filtrate, and then perform rotary evaporation on the filtrate (to remove the fluorosilane compound) to obtain a post-evaporation substrate; add a second solvent to the post-evaporation substrate for dissolution, and after filtering to remove the residual ammonium salt, obtain a 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane solution; preferably, in this step S30, the second solvent is any one or a mixture of several of polar solvents or non-polar solvents; among them, the polar solvents are any one or a mixture of several of methanol, ethanol, n-propanol, isopropanol, acetone, butanone, ethyl acetate, propyl acetate, dichloromethane, chloroform, 1,2-dichloroethane, dimethyl sulfoxide, N,N-dimethylformamide, ether, tetrahydrofuran, and 1,4-dioxane; the non-polar solvents are any one or a mixture of several of benzene, toluene, xylene, cyclohexane, n-hexane, and n-heptane; the addition amount of the second solvent is 2 to 10 times the weight of the post-evaporation substrate. Preferably, in order to obtain pure 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane, in this embodiment, after step S30, the following step S40 is further included: Perform rotary evaporation on the 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane solution obtained in the above step S30); then stir and crystallize the rotary evaporation substrate under low temperature conditions (-15 to -5 °C, more preferably -11 to -9 °C), and obtain a 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane product after filtration.

[0020] In order to enable those skilled in the art to better understand the technical solutions in the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative efforts shall fall within the protection scope of the present invention.

[0021] On the basis of the above-described implementation schemes, the present application further proposes the following specific embodiments: It should be noted that the reagent raw materials used in the following specific embodiments of the present invention are all ordinary commercially available products.

[0022] Example 1: According to the following operation process: S10. Add 770 ml of dichloromethane to a 1000 ml reaction flask, control the temperature of the reaction flask at 10°C, introduce 52 g (0.5 mol) of phosphorus oxyfluoride gas into the reaction flask, and then dropwise add 101 g (0.49 mol) of 1,2-bis(trimethylsilyloxy)ethane to the reaction flask over a period of 4 hours. During the addition of 1,2-bis(trimethylsilyloxy)ethane, control the stirring speed in the reaction flask at 500 r / min. After the addition is complete, continue to react at this temperature for 2 hours and then raise the temperature to 39°C for the first heat preservation reaction for 5 hours to obtain a crude solution of 2-fluoro-2-oxo-1,3,2-dioxaphospholane; S20. Control the temperature of the reaction flask at -10°C, and slowly dropwise add 500 ml of a dimethylamine-tetrahydrofuran solution (dimethylamine concentration is 2 mol / L) to the reaction flask containing the above-mentioned crude solution of 2-fluoro-2-oxo-1,3,2-dioxaphospholane. After the addition is complete, raise the temperature of the reaction flask to 20°C for the second heat preservation reaction for 5 hours to obtain a reaction solution of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane; S30. Filter the reaction solution of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane to obtain a filtrate, and perform rotary evaporation on the filtrate at a temperature not higher than 50°C until it becomes viscous to obtain a post-evaporation substrate. Add 500 ml of ether to the post-evaporation substrate for dissolution and extraction, and after filtering to remove residual ammonium salts, obtain an ether solution of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane; S40. Perform rotary evaporation on the ether solution of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane until it becomes turbid, and stop the rotary evaporation. Then, carry out stirring crystallization at -10°C for 5 hours, and after filtration, obtain 59.5 g of white crystal compound of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane as the product, and the product yield is 80.41%.

[0023] In this application, the white crystal compound of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane obtained in Example 1 was subjected to NMR (Nuclear Magnetic Resonance Spectroscopy) using a spectrometer, specifically including 1 H NMR (400MHz), 13 C NMR (100 MHz), and the characterization results are as follows: 1 H NMR (CDCN 3 , ppm): δ 4.26−4.32 (OCH2CH2O), 2.64 (3H), 2.61 (3H). 13 13C NMR (CDCl3, ppm): δ 66.1 (OCH2CH2O), 35.77 (CH3), 35.72 (CH3).

[0024] Example 2: The following operation process was carried out: S10: Add 770 ml of tetrahydrofuran to a 1000 ml reaction flask, control the temperature of the reaction flask at 10 °C, introduce 52 g (0.5 mol) of phosphorus oxychloride trifluoride gas into the reaction flask, and then dropwise add 101 g (0.49 mol) of 1,2-bis(trimethylsilyloxy)ethane to the reaction flask. During the dropwise addition of 1,2-bis(trimethylsilyloxy)ethane, control the stirring speed in the reaction flask at 500 r / min, and the dropping time is 4 hours; after the dropwise addition is completed, continue to react at this temperature for 2 hours and then raise the temperature to 50 °C for the first heat preservation reaction for 5 hours to obtain a crude product solution of 2-fluoro-2-oxo-1,3,2-dioxaphospholane; S20: Control the temperature of the reaction flask at -10 °C, and slowly dropwise add 500 ml of dimethylamine-tetrahydrofuran solution (dimethylamine concentration is 2 mol / L) to the reaction flask containing the above-mentioned crude product solution of 2-fluoro-2-oxo-1,3,2-dioxaphospholane; after the dropwise addition is completed, raise the temperature of the reaction flask to 20 °C for the second heat preservation reaction for 5 hours to obtain a reaction solution of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane; S30: Filter the reaction solution of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane to obtain a filtrate, and perform rotary evaporation on the filtrate at a temperature not higher than 50 °C until it becomes viscous to obtain a post-evaporation substrate; add 500 ml of ether to the post-evaporation substrate for dissolution and extraction, and after filtering to remove residual ammonium salts, obtain an ether solution of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane; S40: Perform rotary evaporation on the ether solution of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane until it becomes turbid, and stop the rotary evaporation; then stir and crystallize at a temperature of -10 °C for 5 hours, and after filtration, obtain 56.3 g of white crystal compound of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane as the product, and the product yield is 76.1%.

[0025] Example 3: The following operation process was carried out: S10. Add 770 ml of tetrahydrofuran to a 1000-ml reaction flask, control the temperature of the reaction flask at 10°C, introduce 52 g (0.5 mol) of phosphorus oxychloride trifluoride gas into the reaction flask, and then dropwise add 101 g (0.49 mol) of 1,2-bis(trimethylsilyloxy)ethane to the reaction flask. During the dropping of 1,2-bis(trimethylsilyloxy)ethane, control the stirring speed in the reaction flask at 500 r / min, and the dropping time is 4 hours. After the dropping is completed, continue to react at this temperature for 2 hours and then raise the temperature to 35°C for the first heat preservation reaction for 5 hours to obtain a crude solution of 2-fluoro-2-oxo-1,3,2-dioxaphospholane; S20. Control the temperature of the reaction flask at -10°C, and slowly dropwise add 500 ml of dimethylamine-tetrahydrofuran solution (dimethylamine concentration is 2 mol / L) to the reaction flask containing the above-mentioned crude solution of 2-fluoro-2-oxo-1,3,2-dioxaphospholane. After the dropping is completed, raise the temperature of the reaction flask to 20°C for the second heat preservation reaction for 5 hours to obtain a reaction solution of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane; S30. Filter the reaction solution of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane to obtain a filtrate, and perform rotary evaporation on this filtrate at a temperature not higher than 50°C until it becomes viscous to obtain a post-evaporation substrate. Add 500 ml of methyl tert-butyl ether (MTBE) to the post-evaporation substrate for dissolution and extraction. After filtering to remove the residual ammonium salts, obtain an MTBE solution of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane; S40. Perform rotary evaporation on the MTBE solution of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane until it becomes turbid, and stop the rotary evaporation. Then, perform stirring crystallization at -10°C for 5 hours, and after filtration, obtain 62 g of white crystal compound of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane as the product, and the product yield is 86.12%.

[0026] Example 4: The rest of the technical solutions of this Example 4 are the same as those of Example 1, except that in step S10 of this Example 4, after the dropping is completed, continue to react at this temperature for 2 hours and then raise the temperature to 60°C for the first heat preservation reaction for 5 hours; The product yield obtained in this Example 4 is 63.47%.

[0027] Example 5: The rest of the technical solutions of this Example 5 are the same as those of Example 1, except that in step S10 of this Example 5, after the dropping is completed, continue to react at this temperature for 2 hours and then raise the temperature to 30°C for the first heat preservation reaction for 5 hours; The product yield obtained in this Example 5 is 83.57%.

[0028] Comparative Example 1: The rest of the technical solutions of this Comparative Example 1 are the same as those of Example 1, except that step S10 of this Comparative Example 1 is as follows: Add 76.5 g (0.5 mol) of phosphorus oxychloride and 770 ml of dichloromethane into a 1000 ml reaction flask, and control the temperature of the reaction flask at -30 °C; then add 31 g (0.5 mol) of ethylene glycol dropwise to the reaction flask, and the dropping time is 4 hours; control the stirring speed in the reaction flask at 500 r / min during the dropping of ethylene glycol; after the dropping is completed, continue to react at this temperature for 2 hours and then raise the temperature to 20 °C for the first heat preservation reaction for 5 hours to obtain a crude product solution of 2-chloro-2-oxo-1,3,2-dioxaphospholane; then replace the crude product solution of 2-fluoro-2-oxo-1,3,2-dioxaphospholane in step S20 with the crude product solution of 2-chloro-2-oxo-1,3,2-dioxaphospholane obtained in this step S10; This Comparative Example 1 finally obtained 43 g of white crystal compound of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane as the product, and the product yield was 57.04%.

[0029] Comparative Example 2: The rest of the technical solutions of this Comparative Example 2 are the same as those of Example 1, except that step S10 of this Comparative Example 1 is as follows: Add 76.5 g (0.5 mol) of phosphorus oxychloride and 770 ml of tetrahydrofuran into a 1000 ml reaction flask, and control the temperature of the reaction flask at -5 °C; then add 31 g (0.5 mol) of ethylene glycol dropwise to the reaction flask, control the stirring speed in the reaction flask at 500 r / min during the dropping of ethylene glycol, and the dropping time is 4 hours; after the dropping is completed, continue to react at this temperature for 2 hours and then raise the temperature to 20 °C for the first heat preservation reaction for 5 hours to obtain a crude product solution of 2-chloro-2-oxo-1,3,2-dioxaphospholane; then replace the crude product solution of 2-fluoro-2-oxo-1,3,2-dioxaphospholane in step S20 with the crude product solution of 2-chloro-2-oxo-1,3,2-dioxaphospholane obtained in this step S10; This Comparative Example 2 finally obtained 28 g of white crystal compound of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane as the product, and the product yield was 37.14%.

[0030] Comparative Example 3: The remaining technical solutions of this Comparative Example 3 are the same as those of Example 1, except that step S10 of this Comparative Example 1 is as follows: Add 76.5 g (0.5 mol) of phosphorus oxychloride and 770 ml of tetrahydrofuran to a 1000 ml reaction flask, and control the temperature of the reaction flask at -30°C; then add 31 g (0.5 mol) of ethylene glycol dropwise to the reactor, and control the stirring speed in the reaction flask at 500 r / min during the addition of ethylene glycol, and the dropping time is 4 hours; after the dropping is completed, continue to react at this temperature for 2 hours and then raise the temperature to 20°C for the first heat preservation reaction for 5 hours to obtain a crude solution of 2-chloro-2-oxo-1,3,2-dioxaphospholane;; Then, the crude solution of 2-chloro-2-oxo-1,3,2-dioxaphospholane obtained in this step S10 is used to replace the crude solution of 2-fluoro-2-oxo-1,3,2-dioxaphospholane in step S20; This Comparative Example 3 finally obtained 48 g of white crystal compound of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane as the product, and the product yield was 63.66%.

[0031] For those skilled in the art, it is obvious that the present invention is not limited to the details of the above exemplary embodiments, and the present invention can be implemented in other specific forms without departing from the spirit or basic characteristics of the present invention. Therefore, from any point of view, the embodiments should be regarded as exemplary and non-limiting. The scope of the present invention is defined by the appended claims rather than the above description. Therefore, all changes falling within the meaning and scope of the equivalent elements of the claims are intended to be included in the present invention. Any reference signs in the claims should not be regarded as limiting the claimed claim.

[0032] In addition, it should be understood that although this specification is described according to embodiments, not every embodiment only contains an independent technical solution. This narrative way of the specification is only for clarity. Those skilled in the art should regard the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A method for synthesizing 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane, characterized in that, It includes the following operation steps: S10: Add phosphorus oxychloride and the first solvent into the reaction device respectively. Dropwise add 1,2-bis(trimethylsilyloxy)ethane into the reaction device for preliminary reaction, and then raise the temperature for the first heat preservation reaction to obtain an intermediate reaction solution. S20: Dropwise add a dimethylamine solution into the reaction device of the intermediate reaction solution obtained in the above step S10 for the second heat preservation reaction to obtain a 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane reaction solution. S30: Filter the 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane reaction solution obtained in the above step S20 to obtain a filtrate, and then perform rotary evaporation on the filtrate to obtain an evaporated substrate. Add a second solvent to the evaporated substrate for dissolution, and after filtering to remove residual ammonium salts, obtain a 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane solution.

2. The synthesis method of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane according to claim 1, characterized in that, In the step S10, the dropping time of the 1,2-bis(trimethylsilyloxy)ethane is 2 - 6 hours, preferably 4 - 5 hours; when dropping the 1,2-bis(trimethylsilyloxy)ethane, the temperature of the reaction device is controlled at -10 to 20°C, more preferably 10 to 20°C; the temperature of the first heat preservation reaction is set at 20 - 100°C, more preferably 30 - 45°C; the reaction time of the heat preservation reaction is 5 - 10 hours, more preferably 8 - 10 hours.

3. The synthesis method of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane according to claim 1, characterized in that, In the step S10, the molar ratio of the phosphorus oxychloride to the 1,2-bis(trimethylsilyloxy)ethane in the feed is 1:0.9 - 1.2, more preferably 1:0.95 - 1.

4. The synthesis method of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane according to claim 1, characterized in that, In the step S10, the first solvent is any one or a mixture of several of polar solvents or non-polar solvents; among them, the polar solvents are any one or a mixture of several of acetone, butanone, ethyl acetate, propyl acetate, dichloromethane, chloroform, 1,2-dichloroethane, dimethyl sulfoxide, N,N-dimethylformamide, tetrahydrofuran and 1,4-dioxane; the non-polar solvents are any one or a mixture of several of benzene, toluene, xylene, cyclohexane, n-hexane and n-heptane; the dosage of the first solvent is 5 - 20 times the weight of the 1,2-bis(trimethylsilyloxy)ethane.

5. The synthesis method of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane according to claim 1, characterized in that, In the step S20, when dropping the dimethylamine solution, the temperature of the reaction device is controlled at -10 to 10°C, more preferably -10 to -5°C; the temperature of the second heat preservation reaction is set at 0 - 30°C, more preferably 20 - 30°C; the reaction time of the second heat preservation reaction is 3 - 10 hours, more preferably 4 - 8 hours.

6. The synthesis method of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane according to claim 1, characterized in that, In the step S20, the dimethylamine solution is any one or a mixture of several of dimethylamine-tetrahydrofuran solution, dimethylamine-dioxane solution and dimethylamine-methanol solution; the concentration of the dimethylamine solution is 1.5 - 2.5 mol / L.

7. The synthesis method of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane according to claim 1, characterized in that, In the step S20, the molar ratio of the dimethylamine in the dimethylamine solution to the phosphorus oxychloride is 0.9 - 2.5:1, more preferably 1.5 - 2:

1.

8. The synthesis method of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane according to claim 1, characterized in that, In the step S30, the second solvent is any one or a mixture of several of polar solvents or non-polar solvents; wherein, the polar solvent is any one or a mixture of several of methanol, ethanol, n-propanol, isopropanol, acetone, butanone, ethyl acetate, propyl acetate, dichloromethane, chloroform, 1,2-dichloroethane, dimethyl sulfoxide, N,N-dimethylformamide, ether, tetrahydrofuran and 1,4-dioxane; the non-polar solvent is any one or a mixture of several of benzene, toluene, xylene, cyclohexane, n-hexane and n-heptane.

9. The synthesis method of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane according to claim 1, characterized in that, In the step S30, the addition amount of the second solvent is 2-10 times the weight of the substrate after evaporation.

10. The synthesis method of 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane according to claim 1, characterized in that, After the step S30, the following step S40 is further included: The 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane solution obtained in the above step S30 is subjected to rotary evaporation; then the rotary evaporation substrate is stirred and crystallized under low temperature conditions, and the 2-dimethylamino-2-oxo-1,3,2-dioxaphospholane product is obtained after filtration.

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