Synthesis process of (E)-3-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborane-2-yl) ethyl acrylate

Abstract

The invention relates to the technical field of medical intermediates, and particularly discloses a synthesis process of (E)-3-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborane-2-yl) ethyl acrylate, which comprises the following steps: adding cuprous chloride, sodium tert-butoxide and 4, 5-bis (diphenylphosphine)-9, 9-dimethyl xanthene into THF (tetrahydrofuran), introducing N2 to continuously purge, and stirring at 25 DEG C; dissolving bis (pinacolato) diboron in THF (tetrahydrofuran), slowly dropwise adding into the reaction system, and adding ethyl propiolate and methanol while stirring; and finally, heating the reaction mixture to room temperature, stirring overnight, filtering out insoluble solids, concentrating filtrate, separating an organic layer, washing with saline water, drying with sodium sulfate, performing reduced pressure distillation, passing through a column by using petroleum ether and petroleum ether-ethyl acetate as eluents, and spin-drying a solvent to obtain the (E)-3-(4, 4, 5, 5-tetramethyl-1, 3, 4, 5, 5-tetramethyl-1, 3, 5, 6-tetramethyl-1, 3, 5, 6-tetramethyl-1, 3, 6-tetramethyl-1, 3, 6-tetramethyl-1, 3, 6-tetramethyl-1, 3, 6-tetramethyl-1, 3, 6-tetramethyl-1, the invention relates to a 2, 2-dioxaborane-2-yl) ethyl acrylate product. According to the application of the synthesis process disclosed by the invention, the (E)-3-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborane-2-yl) ethyl acrylate product with relatively high purity can be obtained.

Description

Technical Field

[0001] The present application relates to the technical field of pharmaceutical intermediates, and more specifically, it relates to a synthesis process of ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate. Background Art

[0002] Ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate, also known as dimethylbutanediol 2-(ethoxycarbonyl)vinylacetate or pinacol 2-ethoxycarbonylvinyldiboronate, is an organic boronic ester, and organic boronic esters are an important class of pharmaceutical intermediates and organic chemical reagents, and are commonly used in the following aspects: (1) As a reagent and catalyst for organic synthesis reactions.

[0003] (2) For constructing organic molecules and complexes, such as C-C bond formation reactions in organic synthesis, C-H bond functionalization reactions in organic synthesis, etc.

[0004] (3) For the synthesis of heterocyclic compounds.

[0005] In drug discovery, scientists often need to obtain some molecules with novel structures and good activities. During the molecular modification process, double bonds or carboxylic acids are often introduced to increase the affinity between the molecule and the protein and the molecular binding. Through the pharmaceutical intermediate ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (cas: 1009307-13-4), scientists can easily achieve the goal, and its structure is as follows: Only one halogen or halogen-like (OTf) group is required on its parent structure, and similar derivatives can be obtained through the Suzuki reaction.

[0006] Generally, in the synthesis of ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate, copper(I) chloride, sodium tert-butoxide, and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene are added to THF, purged continuously with N2, and stirred at 25 °C. Then, bis(pinacolato)diboron is dissolved in THF and slowly added dropwise to the above reaction system, and then ethyl propiolate and methanol are added with stirring. Finally, the reaction mixture is heated to room temperature and stirred overnight, the insoluble solids are filtered off, the filtrate is concentrated, the organic layer is separated, washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo to obtain.

[0007] Regarding the related technologies mentioned above, the inventor believes that for the use of pharmaceutical intermediates, high-purity intermediates can often reduce the impact of impurities on subsequent drug synthesis, lower the impurity content in drugs, and thus improve the quality and stability of drugs. However, in the industrial scale-up production of the synthesis of the above-mentioned ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate, it is often difficult to achieve a high purity, resulting in limited application of the obtained ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate product. Therefore, there is an urgent need to propose a solution to solve the above technical problems. Summary of the Invention

[0008] In order to improve the purity of the ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate product, the present application provides a synthesis process for ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate.

[0009] The synthesis process for ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate provided by the present application adopts the following technical scheme: A synthesis process for ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate, comprising the following steps: (1) In a reaction kettle, nitrogen is continuously purged, copper chloride, sodium tert-butoxide, 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene and THF are added, and stirred at 25 °C to form a reaction system; then bis(pinacolato)diboron is dissolved in THF and added dropwise to the reaction system in batches slowly, with the temperature maintained at 25 °C; after stirring, ethyl propiolate and methanol are added, and the obtained reaction mixture is stirred overnight in nitrogen at 25 °C; (2) After monitoring the completion of the reaction by TLC, the solvent is removed by rotary evaporation, the obtained crude product is left standing overnight, filtered by suction, the filter cake is washed with ethyl acetate, and the filtrate is collected; then the filtrate is extracted with ethyl acetate and water, and the organic phase is washed with saturated sodium chloride solution, anhydrous sodium sulfate is added to dry the organic phase and concentrated to obtain a semi-finished product; (3) After subjecting the semi-finished product obtained in step (2) to vacuum distillation, it is left standing overnight, then filtered by suction, and the filtrate is collected; then the filtrate is passed through a column using petroleum ether and petroleum ether-ethyl acetate as eluents, and the solvent is evaporated to dryness to obtain the ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate product.

[0010] By adopting the above technical solution, after obtaining the semi-finished product by conventional methods, vacuum distillation is first carried out. By reducing the pressure in the system to lower the boiling point of the liquid, the boiling point difference of each component in the semi-finished product can be increased, which is particularly useful for those substances that decompose, oxidize or polymerize before reaching the boiling point during distillation under normal pressure, and low-boiling impurities can be removed. Then, petroleum ether and petroleum ether-ethyl acetate are used as eluents to pass through the column. Due to the different binding forces of various substances in the stationary phase, substances with strong binding forces have a slow elution rate, while substances with weak binding forces have a fast elution rate, thus achieving separation and further improving the purity of the product ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate. At the same time, first pass through a column with pure petroleum ether as the eluent. Utilizing the low polarity of pure petroleum ether, it can interact with different liquids, which can help extract some substances in the mixture, especially those relatively volatile compounds, and assist in washing the impurities in the separation column to ensure the purity of the target compound. Then pass through a column with petroleum ether-ethyl acetate as the eluent. Since petroleum ether has weak polarity and ethyl acetate has medium polarity, polar and non-polar compounds can be separated, thereby optimizing the separation effect of column chromatography and improving the purification degree. And the stepwise elution between the two has an excellent compounding effect, which can effectively remove impurities and obtain a product of ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate with a higher purity.

[0011] Preferably, step (1) is specifically set as follows: In a 100 L reaction kettle, nitrogen is continuously purged, 151.38 g of copper chloride, 440.83 g of sodium tert-butoxide, 884.74 g of 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene and 40 L of THF are added, and a reaction system is formed by stirring at 25 °C. Then, 12942.92 g of bis(pinacolato)diboron is dissolved in 30 L of THF and slowly added dropwise to the reaction system in batches while maintaining the temperature at 25 °C. After stirring, 5000 g of ethyl propiolate and 2.8 L of methanol are added, and the reaction mixture is stirred overnight in nitrogen at 25 °C.

[0012] By adopting the above technical solution, the proportion of raw material usage directly affects the final quality of the product. In the synthesis preparation, the combination of the above-mentioned raw material dosages can obtain a relatively appropriate reaction rate during the reaction process, and to a certain extent, can reduce the generation amount of impurities, thereby ensuring that the obtained product has a high yield and purity.

[0013] Preferably, step (2) is specifically set as follows: after monitoring the completion of the reaction by TLC, the solvent is removed by rotary evaporation. The obtained crude product is left standing overnight at 2-8 °C, then filtered by suction. The filter cake is washed with ethyl acetate, and the filtrate is collected. Then the filtrate is extracted with ethyl acetate and water, and the organic phase is washed with saturated sodium chloride solution. Anhydrous sodium sulfate is added to dry the organic phase and concentrated to obtain a semi-finished product.

[0014] Preferably, step (3) is specifically set as follows: after vacuum distillation of the semi-finished product obtained in step (2), it is left standing overnight at 2-8 °C, then filtered by suction, and the filtrate is collected. Then the filtrate is passed through a column using petroleum ether and petroleum ether-ethyl acetate as eluents, and the solvent is evaporated to dryness to obtain ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate.

[0015] By adopting the above technical solution, many reactions require a certain amount of time to complete. Standing overnight can ensure that the reactants have sufficient time for complete reaction, and can also help remove unreacted raw materials and by-products, making the product purer. Controlling the temperature at 2-8 °C during the overnight standing treatment can not only achieve the above-mentioned better application effects, but also ensure the stability of the obtained reaction product.

[0016] Preferably, step (3) is specifically set as follows: after vacuum distillation of the semi-finished product obtained in step (2), it is left standing overnight, then filtered by suction, and the filtrate is collected. Then the filtrate is passed through a column using petroleum ether and petroleum ether-ethyl acetate as eluents, and the solvent is evaporated to dryness to obtain a crude product. The crude product is left standing overnight at 8 °C, then filtered by suction, and the filtrate is collected. Then the filtrate is left standing overnight at -20 °C, then filtered by suction, and the filtrate is collected. Finally, the filtrate is left standing at -40 °C for 4 h, then filtered by suction to obtain ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate.

[0017] By adopting the above technical solution, the obtained crude product often contains bis(pinacolato)diboron. Performing the overnight treatment with the above temperature gradient can gradually precipitate white solids, and the precipitation is relatively complete during the standing treatment at 8 °C, -20 °C and -40 °C, further improving the purity of ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate.

[0018] Preferably, in step (2), the operation of vacuum distillation is carried out with a pressure range of 1.3-2.0 kPa, a time of 30-60 min, and a temperature of 70-80 °C.

[0019] Preferably, in step (2), the operating temperature of vacuum distillation is 75 °C.

[0020] By adopting the above technical solution, vacuum distillation can be carried out at a lower temperature, and the selection of the above temperature avoids decomposition, polymerization or oxidation reactions that may be caused by high temperature, thereby protecting the purity and activity of the target product.

[0021] Preferably, in step (3), the volume ratio of petroleum ether to ethyl acetate in the petroleum ether-ethyl acetate eluent is (18-22):1.

[0022] Preferably, in step (3), the volume ratio of petroleum ether to ethyl acetate in the petroleum ether-ethyl acetate eluent is 20:1.

[0023] By adopting the above technical solution, the ratio of petroleum ether to ethyl acetate is crucial. A suitable ratio can improve the solubility of the compound, thereby improving the separation effect, and the above volume ratio of petroleum ether to ethyl acetate can bring a better separation effect on the sample, which is beneficial to ensuring the obtainment of ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate with a higher purity.

[0024] Preferably, in each step of the operation, the time for overnight treatment is 8-10h.

[0025] In summary, the present application has the following beneficial effects: In the present application, the semi-finished product obtained by a conventional method is first subjected to vacuum distillation, and then petroleum ether and petroleum ether-ethyl acetate are used as eluents to pass through a column, which can effectively remove impurities and further improve the purity of ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate; at the same time, white solids can be gradually precipitated during the treatment of the crude product at 8°C, -20°C and -40°C, which is beneficial to further obtaining ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate with a higher purity. Detailed implementation manners

[0026] The present application will be further described in detail below with reference to examples and comparative examples. Examples

[0027] Example 1 A synthesis process of ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate, comprising the following steps: (1) In a 100 L reaction kettle, nitrogen was introduced for continuous purging. 151.38 g of cuprous chloride, 440.83 g of sodium tert-butoxide, 884.74 g of 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, and 40 L of THF were added, and the mixture was stirred at 25 °C for 2 h to form a reaction system. Then, 12942.92 g of bis(pinacolato)diboron was dissolved in 30 L of THF and slowly added dropwise to the reaction system in batches while maintaining the temperature at 25 °C. After stirring for another 30 min, 5000 g of ethyl propiolate and 2.8 L of methanol were added, and the resulting reaction mixture was stirred overnight under nitrogen at 25 °C; (2) After monitoring the completion of the reaction by TLC, the solvent was removed by rotary evaporation. The obtained crude product was left standing overnight at 2 - 8 °C (preferably 5 °C in this example), then filtered by suction, and the filter cake was washed with ethyl acetate, and the filtrate was collected. Then, the filtrate was extracted with ethyl acetate and water, and the organic phase was washed with saturated sodium chloride solution. Anhydrous sodium sulfate was added to dry the organic phase and concentrated to obtain a semi-finished product; (3) After vacuum distillation of the semi-finished product obtained in step (2), it was left standing overnight at 2 - 8 °C (preferably 5 °C in this example), then filtered by suction, and the filtrate was collected. Then, the filtrate was passed through a column using petroleum ether and petroleum ether - ethyl acetate as eluents, and the solvent was evaporated to dryness to obtain the product ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate.

[0028] Note: The time for overnight treatment in the above operations is 8 - 10 h, and 10 h was selected in this example; in step (2), the operation of vacuum distillation was carried out with a pressure range of 1.65 kPa, a time of 45 min, and a temperature of 75 °C; the volume ratio of petroleum ether to ethyl acetate in the petroleum ether - ethyl acetate eluent was 20:1.

[0029] Example 2 A synthetic process of ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate, which is different from Example 1 in that in step (2), the operation of vacuum distillation was carried out with a pressure range of 1.3 kPa, a time of 60 min, and a temperature of 70 °C.

[0030] Example 3 A synthetic process of ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate, which is different from Example 1 in that in step (2), the operation of vacuum distillation was carried out with a pressure range of 2.0 kPa, a time of 30 min, and a temperature of 80 °C.

[0031] Example 4 A synthetic process of ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate, which is different from that of Example 1 in that in step (3), the volume ratio of petroleum ether to ethyl acetate in the petroleum ether-ethyl acetate eluent is 18:1.

[0032] Example 5 A synthetic process of ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate, which is different from that of Example 1 in that in step (3), the volume ratio of petroleum ether to ethyl acetate in the petroleum ether-ethyl acetate eluent is 22:1.

[0033] Example 6 A synthetic process of ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate, which is different from that of Example 1 in that step (3) is specifically set as follows: after subjecting the semi-finished product obtained in step (2) to vacuum distillation, it is left standing overnight, then filtered by suction, and the filtrate is collected; then the filtrate is passed through a column using petroleum ether and petroleum ether-ethyl acetate as eluents, the solvent is evaporated to dryness to obtain a crude product; the crude product is left standing overnight at 8 °C, filtered by suction, the filtrate is collected, and then the filtrate is left standing overnight at -20 °C, filtered by suction, the filtrate is collected, and finally the filtrate is left standing at -40 °C for 4 h, filtered by suction to obtain the ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate product.

[0034] Comparative example Comparative example 1 A synthetic process of ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate, which is different from that of Example 1 in that step (3) is specifically set as follows: after subjecting the semi-finished product obtained in step (2) to vacuum distillation, it is left standing overnight at 2-8 °C (preferably 5 °C in this example), then filtered by suction to obtain the ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate product.

[0035] Comparative example 2 A synthetic process of ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate, which is different from that of Example 1 in that step (3) is specifically set as follows: after passing the semi-finished product obtained in step (2) through a column using petroleum ether and petroleum ether-ethyl acetate as eluents, the solvent is evaporated to dryness to obtain the ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate product.

[0036] Comparative Example 3 A synthetic process for ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate, which is different from Example 1 in that step (3) is specifically set as follows: after subjecting the semi-finished product obtained in step (2) to vacuum distillation, it is left standing overnight at 2-8 °C (preferably 5 °C in this example), then subjected to suction filtration, and the filtrate is collected; then the filtrate is passed through a column using petroleum ether as the eluent, and the solvent is evaporated to dryness to obtain the ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate product.

[0037] Comparative Example 4 A synthetic process for ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate, which is different from Example 1 in that step (3) is specifically set as follows: after subjecting the semi-finished product obtained in step (2) to vacuum distillation, it is left standing overnight at 2-8 °C (preferably 5 °C in this example), then subjected to suction filtration, and the filtrate is collected; then the filtrate is passed through a column using petroleum ether-ethyl acetate as the eluent, and the solvent is evaporated to dryness to obtain the ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate product.

[0038] Comparative Example 5 A synthetic process for ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate, which is different from Example 1, includes the following steps: (1) In a 100 L reaction kettle, nitrogen is continuously purged, 151.38 g of copper chloride, 440.83 g of sodium tert-butoxide, 884.74 g of 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene and 40 L of THF are added, and the mixture is stirred at 25 °C for 2 h to form a reaction system; then 12942.92 g of bis(pinacolato)diboron is dissolved in 30 L of THF and slowly added dropwise to the reaction system in batches while maintaining the temperature at 25 °C; after stirring for another 30 min, 5000 g of ethyl propiolate and 2.8 L of methanol are added, and the reaction mixture is stirred overnight in nitrogen at 25 °C; (2) After monitoring the completion of the reaction by TLC, the solvent is removed by rotary evaporation, the obtained crude product is left standing overnight at 2-8 °C (preferably 5 °C in this example), subjected to suction filtration, the filter cake is washed with ethyl acetate, and the filtrate is collected; then the filtrate is extracted with ethyl acetate and water, the organic phase is washed with saturated sodium chloride solution, anhydrous sodium sulfate is added to dry the organic phase and concentrated to obtain the ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate product.

[0039] Performance detection test Test samples: Ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate prepared by applying Examples 1-6 was used as Test Samples 1-6, and Ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate prepared by applying Comparative Examples 1-5 was used as Control Samples 1-5.

[0040] Test method: Calculate the purity of Test Samples 1-6 and Control Samples 1-5. Purity = mass of pure substance / total mass of mixture × 100% = mass of pure substance / (mass of pure substance + mass of impurities) × 100% = 1 - mass fraction of impurities, and record the test results correspondingly in Table 2.

[0041] Table 2 Test results of Test Samples 1-6 and Control Samples 1-5 Sample Purity (%) Test Sample 1 99.5 Test Sample 2 99.0 Test Sample 3 99.2 Test Sample 4 99.1 Test Sample 5 99.3 Test Sample 6 99.8 Control Sample 1 89.5 Control Sample 2 89.7 Control Sample 3 91.1 Control Sample 4 91.4 Control Sample 5 85.6 Combined with Examples 1-5 and Comparative Examples 1-5 and combined with Table 2, it can be seen that by first performing vacuum distillation on the semi-finished products prepared by conventional methods, and then passing the column using petroleum ether and petroleum ether-ethyl acetate as eluents, impurities can be effectively removed, and the purity of the Ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate product can be further improved. At the same time, if only vacuum distillation is performed or the column is passed using petroleum ether and petroleum ether-ethyl acetate as eluents, although the purity of the Ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate product can be improved, the improvement effect is limited, and it is far less excellent than the effect brought by the combination of the two operations. Further, if only petroleum ether is used as the eluent for passing the column or only petroleum ether-ethyl acetate is used as the eluent for passing the column, the corresponding effect brought by the column passing operation will also be greatly reduced.

[0042] Combined with Example 1 and Example 6 and combined with Table 2, it can be seen that white solids can gradually precipitate during the process of placing the crude product at 8°C, -20°C and -40°C, which is beneficial to further obtaining a higher purity Ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate product.

[0043] This specific embodiment is only an interpretation of the present application, and it is not a limitation of the present application. Those skilled in the art can make modifications without creative contributions to this embodiment according to needs after reading this specification, but as long as they are within the scope of the claims of the present application, they are protected by the patent law.

Claims

1. A process for synthesizing (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethyl acrylate, characterized in that: The following steps are involved: (1) In a reaction kettle, nitrogen is introduced and continuously purged, cuprous chloride, sodium tert-butoxide, 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene and THF are added, and stirred at 25° C. to form a reaction system; then, diboric acid pinacol ester is dissolved in THF, and slowly added dropwise to the reaction system in batches, and the temperature is maintained at 25° C.; after stirring, ethyl propiolate and methanol are added, and the reaction mixture is stirred and treated overnight in nitrogen at 25° C.; (2) After the reaction is completed by monitoring by TLC, the solvent is removed by rotary evaporation, the obtained crude product is left to stand overnight, filtered, the filter cake is washed with ethyl acetate, and the filtrate is collected; the filtrate is then extracted with ethyl acetate and water, the organic phase is washed with a saturated sodium chloride solution, anhydrous sodium sulfate is added to dry the organic phase, and concentrated to obtain a semi-finished product; (3) The semi-finished product obtained in step (2) is subjected to reduced pressure distillation, left to stand overnight, and then filtered to collect the filtrate; the filtrate is then passed through a column using petroleum ether or petroleum ether-ethyl acetate as an eluent, and the solvent is dried by spin drying to obtain (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) ethyl acrylate product.

2. The synthesis process of (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethyl acrylate according to claim 1, characterized in that: The specific configuration of step (1) is as follows: in a 100 L reactor, nitrogen is introduced and purged continuously, 151.38 g of cuprous chloride, 440.83 g of sodium tert-butoxide, 884.74 g of 4,5-bis(diphenylphosphine)-9,9-dimethylxanthene and 40 L of THF are added, and stirred at 25° C. to form a reaction system; then 12942.92 g of diboric acid pinacol ester is dissolved in 30 L of THF, and slowly added dropwise to the reaction system in batches, and the temperature is maintained at 25° C.; after stirring, 5000 g of ethyl propiolate and 2.8 L of methanol are added to obtain a reaction mixture, which is stirred and treated overnight in nitrogen at 25° C.

3. The synthesis process of (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethyl acrylate according to claim 1, characterized in that: The specific configuration of step (2) is as follows: after the reaction is completed by monitoring by TLC, the solvent is removed by rotary evaporation, the obtained crude product is placed at 2-8° C. overnight for treatment, filtered, the filter cake is washed with ethyl acetate, and the filtrate is collected; the filtrate is then extracted with ethyl acetate and water, the organic phase is washed with a saturated sodium chloride solution, anhydrous sodium sulfate is added to dry the organic phase, and concentrated to obtain a semi-finished product.

4. The synthesis process of (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethyl acrylate according to claim 1, characterized in that: Step (3) is specifically configured as follows: the semi-finished product obtained in step (2) is subjected to reduced pressure distillation, and then placed at 2-8° C. for overnight treatment, and then filtered to collect the filtrate; the filtrate is then passed through a column using petroleum ether or petroleum ether-ethyl acetate as an eluent, and the solvent is dried by spin drying to obtain (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) ethyl acrylate product.

5. The synthesis process of (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethyl acrylate according to claim 1, characterized in that: Step (3) is specifically configured as follows: the semi-finished product obtained in step (2) is subjected to reduced pressure distillation, left to stand overnight, then filtered, and the filtrate is collected; the filtrate is then passed through a column using petroleum ether or petroleum ether-ethyl acetate as an eluent, and the solvent is dried to obtain a crude product; the crude product is left to stand overnight at 8° C., filtered, and the filtrate is collected; the filtrate is then left to stand overnight at -20° C., filtered, and the filtrate is collected; and finally the filtrate is left to stand at -40° C. for 4 hours, filtered, and the (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) ethyl acrylate product is obtained.

6. The synthesis process of (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethyl acrylate according to claim 1, characterized in that: In step (2), the operation of reduced pressure distillation is as follows: the pressure range is 1.3-2.0 kPa, the time is 30-60 min, and the temperature is 70-80°C.

7. The synthesis process of (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethyl acrylate according to claim 6, characterized in that: In step (2), the operating temperature of the reduced pressure distillation is 75°C.

8. The synthesis process of (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethyl acrylate according to claim 1, characterized in that: In step (3), the volume ratio of petroleum ether to ethyl acetate in the petroleum ether-ethyl acetate eluent is (18-22):

1.

9. The synthesis process of (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethyl acrylate according to claim 8, characterized in that: In step (3), the volume ratio of petroleum ether to ethyl acetate in the petroleum ether-ethyl acetate eluent is 20:

1.

10. The synthesis process of (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethyl acrylate according to claim 1, characterized in that: In each step of the operation, the overnight treatment time is 8-10 hours.