Method for synthesizing ethyl 4-cyano-3-hydroxybutyrate by using pure hydrocyanic acid method

Ethyl 4-cyano-3-hydroxybutyrate was synthesized by pure hydrogen cyanide method. The pH of the reaction solution was controlled by a bio-enzyme catalyst, which solved the problem of high sodium hydroxide consumption in the preparation of sodium cyanide, and achieved efficient and low-cost production, with improved product yield and purity.

CN121109518APending Publication Date: 2025-12-12山东宏旭化学股份有限公司 +1
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Patent Information

Application Number
CN202511328856.6
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2025-09-17
Publication Date
2025-12-12

AI Technical Summary

Technical Problem

Existing technologies for preparing ethyl 4-cyano-3-hydroxybutyrate use sodium cyanide as a raw material, resulting in high sodium hydroxide consumption and sodium salt contaminant generation, as well as high costs.

Method used

The pure hydrogen cyanide method was used to synthesize ethyl 4-cyano-3-hydroxybutyrate using ethyl 4-chloro-3-hydroxybutyrate and hydrogen cyanide as raw materials, and biological enzymes as catalysts. The pH of the reaction solution was controlled between 6.5 and 7.5 to avoid the use of sodium cyanide and reduce the consumption of sodium hydroxide.

Benefits of technology

It improved reaction efficiency, shortened reaction time, reduced the cost of treating sodium salt contaminants, lowered production costs, and increased product yield and purity.

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Abstract

The invention provides a method for synthesizing ethyl 4-cyano-3-hydroxybutyrate by a pure hydrocyanic acid method, which is characterized in that ethyl 4-chloro-3-hydroxybutyrate and hydrocyanic acid are used as raw materials, a biological enzyme is used as a catalyst, the pH value of a reaction solution is controlled to be 6.5-7.5, and the ethyl 4-cyano-3-hydroxybutyrate is synthesized; the hydrogen cyanide is used as a raw material, so that the cost of a sodium cyanide preparation process can be reduced, the consumption of sodium hydroxide can be reduced, and the treatment cost of pollutants (sodium salt) can be reduced. The method has the advantages of being high in reasonability, low in material loss and high in production efficiency. The ethyl 4-cyano-3-hydroxybutyrate prepared by the method has the yield of 80%, the content of more than or equal to 98.5% and the single impurity content of less than 0.5%.
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Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of 4-cyano-3-hydroxybutyric acid ethyl ester synthesis, in particular to a method for synthesizing 4-cyano-3-hydroxybutyric acid ethyl ester by pure hydrocyanic acid method. BACKGROUND

[0002] 4-cyano-3-hydroxybutyric acid ethyl ester is an important pharmaceutical intermediate, as the main raw material for atorvastatin synthesis, and has a large demand. At present, sodium cyanide is mainly used as raw material to prepare 4-cyano-3-hydroxybutyric acid ethyl ester, and sodium cyanide provides cyanide and adjusts pH. Sodium cyanide is a product prepared from hydrogen cyanide and sodium hydroxide, and can be transported long distances by taking protective measures.

[0003] In the process of preparing 4-cyano-3-hydroxybutyric acid ethyl ester by using sodium cyanide, not only the consumption of sodium hydroxide is increased, but also sodium salt pollutants are produced. Therefore, it is of great significance to provide a new method for synthesizing 4-cyano-3-hydroxybutyric acid ethyl ester. SUMMARY

[0004] In view of this, the present application provides a method for synthesizing 4-cyano-3-hydroxybutyric acid ethyl ester by pure hydrocyanic acid method. In the method, 4-chloro-3-hydroxybutyric acid ethyl ester and hydrocyanic acid are used as raw materials, and a biological enzyme is used as a catalyst to control the pH of the reaction solution between 6.5 and 7.5 to synthesize 4-cyano-3-hydroxybutyric acid ethyl ester. Using hydrogen cyanide as raw material can avoid the cost of sodium cyanide preparation process, reduce the consumption of sodium hydroxide, and reduce the treatment cost of pollutants (sodium salt).

[0005] The technical scheme of the present application is as follows: A method for synthesizing 4-cyano-3-hydroxybutyric acid ethyl ester by pure hydrocyanic acid method, using 4-chloro-3-hydroxybutyric acid ethyl ester and hydrocyanic acid as raw materials, and a biological enzyme as a catalyst to control the pH of the reaction solution between 6.5 and 7.5 to synthesize 4-cyano-3-hydroxybutyric acid ethyl ester.

[0006] The reaction equation is as follows: .

[0007] In the present application, the pH of the reaction solution is continuously controlled to ensure that the biological enzyme has maximum activity, improve the reaction efficiency, and shorten the reaction time.

[0008] Preferably, the above-mentioned method for synthesizing 4-cyano-3-hydroxybutyric acid ethyl ester by pure hydrocyanic acid method has the following process: (1) Put desalted water into the reaction kettle, then add 4-chloro-3-hydroxybutyric acid ethyl ester to obtain reaction solution A, and control the pH of the reaction solution A between 6.5 and 7.5; (2) adding hydrocyanic acid into the reaction liquid A to obtain reaction liquid B, controlling the temperature of the reaction liquid B during the process of adding hydrocyanic acid and continuously controlling the pH of the reaction liquid B between 6.5-7.5, the adding time of hydrocyanic acid is less than 1.5h, controlling the adding time and adjusting the pH to adjust the reaction environment for the biological enzyme; (3) adjusting the temperature of the reaction liquid B to 35±2℃, adding the biological enzyme into the reaction kettle by a diaphragm pump to obtain reaction liquid C, continuously controlling the temperature of the reaction liquid C between 45-48℃ and the pH between 6.9-7.1 to make the biological enzyme maintain high reaction activity, and obtaining the crude product after the reaction is completed.

[0009] Preferably, in step (1), the pH is adjusted by adding sodium hydroxide solution dropwise into the reaction liquid A.

[0010] Preferably, in step (1), the volume weight (L / kg) ratio of desalted water to ethyl 4-chloro-3-hydroxybutyrate is 3.5-4.5:1.

[0011] Preferably, in step (2), the amount of hydrocyanic acid is added according to the amount of ethyl 4-chloro-3-hydroxybutyrate in step (1); the weight ratio of ethyl 4-chloro-3-hydroxybutyrate to hydrocyanic acid is 10:2.9-3.1; controlling the weight ratio of ethyl 4-chloro-3-hydroxybutyrate to hydrocyanic acid can on one hand control the pH of the reaction liquid to make the biological enzyme maintain high activity and improve the reaction effect, and on the other hand can avoid material waste and reduce the amount of wastewater.

[0012] Preferably, in step (3), sodium hydroxide solution is added dropwise into the reaction liquid C to control the pH.

[0013] Preferably, the crude product is extracted, centrifuged and rectified to obtain a high-purity product.

[0014] Preferably, the reaction system used in the method for synthesizing ethyl 4-cyano-3-hydroxybutyrate by the above pure hydrocyanic acid method comprises a reaction kettle, a sodium hydroxide dropwise adding tank and a biological enzyme tank. The outlet of the sodium hydroxide dropwise adding tank is connected with the inlet A of the reaction kettle, and the outlet of the biological enzyme tank is connected with the inlet B of the reaction kettle. A diaphragm pump is arranged between the biological enzyme tank and the reaction kettle, and the diaphragm pump is used to transport the biological enzyme in the biological enzyme tank to the reaction kettle.

[0015] Preferably, a motor is installed on the reaction kettle, the output shaft of the motor is connected with a stirring paddle, and the free end of the stirring paddle is located in the reaction kettle; a hydrocyanic acid feeding port and a desalted water feeding port are arranged on the side of the reaction kettle, and the feeding can be carried out according to the demand.

[0016] Preferably, a jacket is arranged outside the reaction kettle, and the temperature in the reaction kettle is adjusted by introducing medium at different temperatures.

[0017] The present application has the following advantages over the prior art: 1、The method has the advantages of short flow and high efficiency, and does not use sodium cyanide, which can effectively reduce the discharge of sodium-containing wastewater and improve the safety of production.

[0018] 2、In the present application, hydrocyanic acid is used instead of sodium cyanide, which reduces the preparation process of sodium cyanide, and sodium hydroxide is used to adjust the pH, which effectively reduces the production cost.

[0019] 3、The method has the advantages of high rationality, low material loss and high production efficiency. The 4-cyano-3-hydroxybutyric acid ethyl ester prepared by the method has a yield of >80%, a content of ≥98.5% and a single impurity of <0.5%. BRIEF DESCRIPTION OF DRAWINGS

[0020] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the drawings needed to be used in the embodiments or the prior art description will be briefly introduced. Obviously, for those skilled in the art, other drawings can also be obtained without creative labor based on these drawings.

[0021] Figure 1 It is a schematic diagram of the reaction system of the present application.

[0022] Figure 2 It is HPLC spectrum-1 of sample of Example 4.

[0023] Figure 3 It is HPLC spectrum-2 of sample of Example 4.

[0024] Figure 4 It is HPLC spectrum-1 of sample of Example 5.

[0025] Figure 5 It is HPLC spectrum-2 of sample of Example 5.

[0026] In the figure, 1 is a reaction kettle, 2 is a sodium hydroxide dropping tank, 3 is a biological enzyme tank, 4 is an inlet A, 5 is an inlet B, 6 is a diaphragm pump, 7 is a motor, 8 is a stirring paddle, 9 is a hydrocyanic acid feeding port, 10 is a desalted water feeding port, and 11 is a jacket. DETAILED DESCRIPTION

[0027] In order to make the person skilled in the art better understand the technical solutions in the present application, the technical solutions of the present application will be described clearly and completely in combination with the embodiments of the present application. Obviously, the described embodiments are only some of the embodiments of the present application, not all. Based on the embodiments in the present application, all other embodiments obtained by the person skilled in the art without creative labor should belong to the scope of protection of the present application.

[0028] In the following embodiments of the present application, the biological enzyme manufacturer is Jiangsu Meike Biological Technology Co., Ltd., the sodium hydroxide manufacturer is Dongying Yikesi Petroleum Chemical Industry Co., Ltd., the hydrocyanic acid is self-produced by the company's upstream device with a purity of 99%, and the 4-chloro-3-hydroxybutyric acid ethyl ester is self-produced by the previous process with a purity of 98%.

[0029] In the following embodiments of the present application, the desalted water refers to the pure water obtained by removing suspended solids, colloids, inorganic cations, anions and other impurities in water by water treatment process.

[0030] Embodiment 1 In combination Figure 1 The present application provides a reaction system for a method for synthesizing 4-cyano-3-hydroxybutyric acid ethyl ester by pure hydrocyanic acid method, which comprises a reaction kettle 1, a sodium hydroxide dropping tank 2 and a biological enzyme tank 3. The outlet of the sodium hydroxide dropping tank 2 is connected with the inlet A4 of the reaction kettle 1, and the outlet of the biological enzyme tank 3 is connected with the inlet B5 of the reaction kettle 1. A diaphragm pump 6 is arranged between the biological enzyme tank 3 and the reaction kettle 1, which transports the biological enzyme in the biological enzyme tank 3 to the reaction kettle 1. A motor 7 is installed on the reaction kettle 1, the output shaft of the motor 7 is connected with a stirring paddle 8, and the free end of the stirring paddle 8 is located in the reaction kettle 1; a hydrocyanic acid feeding port 9 and a desalted water feeding port 10 are arranged on the side of the reaction kettle 1, which can feed samples according to the demand; A jacket 11 is arranged outside the reaction kettle 1, which adjusts the temperature in the reaction kettle 1 by passing in medium with different temperatures.

[0031] Embodiment 2 On the basis of embodiment 1, the present application provides a method for synthesizing 4-cyano-3-hydroxybutyric acid ethyl ester by pure hydrocyanic acid method, The reaction equation is as follows: ; The specific reaction process is as follows: (1) Put 4000L of desalted water into a 8000L reactor, then add 1000kg of 4-chloro-3-hydroxybutyric acid ethyl ester, mix well to obtain reaction liquid A, then add sodium hydroxide solution to reaction liquid A, control the pH of reaction liquid A to be 7.0; the concentration of sodium hydroxide solution is 30%; (2) Add 300kg of hydrocyanic acid to reaction liquid A, and the drop of hydrocyanic acid is synchronized with the drop of sodium hydroxide solution, so as to continuously control the pH of the solution in the reactor to be 7.0, after the drop of hydrocyanic acid is completed, use 300 Kg of desalted water to flush the pipeline to obtain reaction liquid B, continuously add sodium hydroxide solution to reaction liquid B, control the pH of reaction liquid B to be 7.0; the drop time of hydrocyanic acid is 1.2h; (3) Use 80℃ water to heat the reaction material, make the temperature of the reactor rise to 35℃, use a diaphragm pump to put 80kg of melted biological enzyme into the reactor, mix well to obtain reaction liquid C; slowly add sodium hydroxide solution to reaction liquid C, continuously control the temperature of reaction liquid C to be 46℃, and the pH to be 7.0, so that the biological enzyme can maintain high reaction activity, when the content of 4-chloro-3-hydroxybutyric acid ethyl ester in reaction liquid C is ≤1%, the reaction is completed, and a crude product is obtained; The yield is 82.3% calculated based on the output of 4-cyano-3-hydroxybutyric acid ethyl ester and the amount of 4-chloro-3-hydroxybutyric acid ethyl ester added, and the content of 4-cyano-3-hydroxybutyric acid ethyl ester in the crude product is 99%, and the single impurity is <0.5%.

[0032] Example 3 Based on example 1, the application provides a method for synthesizing 4-cyano-3-hydroxybutyric acid ethyl ester by pure hydrocyanic acid method, The reaction equation is as follows: ; The specific reaction process is as follows: (1) Put 4000L of desalted water into a 8000L reactor, then add 1000kg of 4-chloro-3-hydroxybutyric acid ethyl ester, mix well to obtain reaction liquid A, then add sodium hydroxide solution to reaction liquid A, control the pH of reaction liquid A to be 7.0; the concentration of sodium hydroxide solution is 30%; (2) Add 300kg of hydrocyanic acid to reaction liquid A, and the drop of hydrocyanic acid is synchronized with the drop of sodium hydroxide solution, so as to continuously control the pH of the solution in the reactor to be 6.5, after the drop of hydrocyanic acid is completed, use 300 Kg of desalted water to flush the pipeline to obtain reaction liquid B, continuously add sodium hydroxide solution to reaction liquid B, control the pH of reaction liquid B to be 6.5; the drop time of hydrocyanic acid is 1.0h; (3) using 80 ℃ water into the jacket heating reaction material, the reactor temperature to 33 ℃, with a diaphragm pump into the molten enzyme 80 kg into the reactor, mix, get reaction liquid C; slowly add sodium hydroxide solution to the reaction liquid C, continuously control the temperature of the reaction liquid C is 45 ℃, pH is 6.9, so that the biological enzyme can maintain high reaction activity, when the content of 4-chloro-3-hydroxybutyric acid ethyl ester in the reaction liquid C ≤1% after the end of the reaction, get crude product; The yield is 80.5% calculated from the output of 4-cyano-3-hydroxybutyric acid ethyl ester and the amount of 4-chloro-3-hydroxybutyric acid ethyl ester added. In the crude product, the content of 4-cyano-3-hydroxybutyric acid ethyl ester is 98.7%, and the single impurity is <0.5%.

[0033] Example 4 Based on example 1, the present application provides a method for synthesizing 4-cyano-3-hydroxybutyric acid ethyl ester by pure hydrocyanic acid method, The reaction equation is as follows: ; The specific reaction process is as follows: (1) 4500L of desalted water was put into a 8000L reactor, then 1000kg of 4-chloro-3-hydroxybutyric acid ethyl ester was added, and after mixing, reaction liquid A was obtained. Add sodium hydroxide solution to the reaction liquid A, control the pH of the reaction liquid A to 7.1; the concentration of sodium hydroxide solution is 30%; (2) 300kg of hydrocyanic acid was added to the reaction liquid A, and the addition of hydrocyanic acid was synchronized with the addition of sodium hydroxide solution, so as to continuously control the pH of the solution in the reactor to 7.1. After the addition of hydrocyanic acid was completed, 300 Kg of desalted water was used to flush the pipeline, and reaction liquid B was obtained. Continue to add sodium hydroxide solution to the reaction liquid B, control the pH of the reaction liquid B to 7.1; the addition time of hydrocyanic acid is 1.4h; (3) using 80 ℃ water into the jacket heating reaction material, the reactor temperature to 35 ℃, with a diaphragm pump into the molten enzyme 80 kg into the reactor, mix, get reaction liquid C; slowly add sodium hydroxide solution to the reaction liquid C, continuously control the temperature of the reaction liquid C is 48 ℃, pH is 7.1, so that the biological enzyme can maintain high reaction activity, when the content of 4-chloro-3-hydroxybutyric acid ethyl ester in the reaction liquid C ≤1% after the end of the reaction, get crude product; The yield is 81.1% calculated from the output of 4-cyano-3-hydroxybutyric acid ethyl ester and the amount of 4-chloro-3-hydroxybutyric acid ethyl ester added. In the crude product, the content of 4-cyano-3-hydroxybutyric acid ethyl ester is 98.9%, and the single impurity is <0.5%.

[0034] Example 5 Based on the embodiment 1, the application provides a method for synthesizing ethyl 4-cyano-3-hydroxybutyrate by pure hydrocyanic acid, The reaction equation is as follows: ; The specific reaction process is as follows: (1) 3700L of desalted water is put into a 8000L reaction kettle, then 1000kg of ethyl 4-chloro-3-hydroxybutyrate is added, after mixing, reaction liquid A is obtained, sodium hydroxide solution is added dropwise into the reaction liquid A, and the pH of the reaction liquid A is controlled to be 7.0; the concentration of the sodium hydroxide solution is 30%; (2) 290kg of hydrocyanic acid is added dropwise into the reaction liquid A, the addition of the hydrocyanic acid is synchronous with the addition of the sodium hydroxide solution, so that the pH of the solution in the reaction kettle is continuously controlled to be 7.0, after the addition of the hydrocyanic acid is completed, 300 Kg of desalted water is used to flush the pipeline, reaction liquid B is obtained, the sodium hydroxide solution is continuously added into the reaction liquid B, and the pH of the reaction liquid B is controlled to be 7.0; the addition time of the hydrocyanic acid is 1.3h; (3) the reaction material is heated by using 80℃ water into the jacket, the temperature of the reaction kettle is increased to 35℃, 80kg of melted biological enzyme is pumped into the reaction kettle by using a diaphragm pump, and then mixing is performed, so that reaction liquid C is obtained; the sodium hydroxide solution is slowly added dropwise into the reaction liquid C, the temperature of the reaction liquid C is continuously controlled to be 45℃, and the pH is controlled to be 7.0, so that the biological enzyme can maintain high reaction activity, when the content of ethyl 4-chloro-3-hydroxybutyrate in the reaction liquid C is ≤1%, the reaction is ended, and a crude product is obtained; According to the output of ethyl 4-cyano-3-hydroxybutyrate and the addition amount of ethyl 4-chloro-3-hydroxybutyrate, the yield is 80.8%, in the crude product, the content of ethyl 4-cyano-3-hydroxybutyrate is 98.9%, and the single impurity is <0.5%.

[0035] Embodiment 6 Based on the embodiment 1, the application provides a method for synthesizing ethyl 4-cyano-3-hydroxybutyrate by pure hydrocyanic acid, The reaction equation is as follows: ; The specific reaction process is as follows: (1) 3700L of desalted water is put into a 8000L reaction kettle, then 1000kg of ethyl 4-chloro-3-hydroxybutyrate is added, after mixing, reaction liquid A is obtained, sodium hydroxide solution is added dropwise into the reaction liquid A, and the pH of the reaction liquid A is controlled to be 7.0; the concentration of the sodium hydroxide solution is 30%; (2) drop 300 kg of hydrocyanic acid into reaction liquid A, the drop of hydrocyanic acid is synchronous with the drop of sodium hydroxide solution, so as to continuously control the pH of the solution in the reaction kettle to be 7.0, after the drop of hydrocyanic acid is completed, use 300 Kg of desalted water to flush the pipeline, obtain reaction liquid B, continuously drop sodium hydroxide solution into reaction liquid B, control the pH of reaction liquid B to be 7.0; the drop time of hydrocyanic acid is 1.4 h; (3) use 80℃ water into the jacket to heat the reaction material, make the temperature of the reaction kettle rise to 35℃, use the diaphragm pump to punch 80 kg of the melted biological enzyme into the reaction kettle, mix uniformly, obtain reaction liquid C; slowly drop sodium hydroxide solution into reaction liquid C, continuously control the temperature of reaction liquid C to be 45℃, the pH is 7.0, so that the biological enzyme can maintain high reaction activity, when the content of 4-chloro-3-hydroxybutyric acid ethyl ester in reaction liquid C is ≤1%, the reaction is completed, obtain the crude product; The yield is 81.9% calculated from the output of 4-cyano-3-hydroxybutyric acid ethyl ester and the added amount of 4-chloro-3-hydroxybutyric acid ethyl ester, in the crude product, the content of 4-cyano-3-hydroxybutyric acid ethyl ester is 99.1%, and the single impurity is <0.5%.

[0036] Example 7 On the basis of example 1, the application provides a method for synthesizing 4-cyano-3-hydroxybutyric acid ethyl ester by pure hydrocyanic acid method, The reaction equation is as follows: ; The specific reaction process is as follows: (1) put 4300 L of desalted water into an 8000 L reaction kettle, then add 1000 kg of 4-chloro-3-hydroxybutyric acid ethyl ester, mix uniformly, obtain reaction liquid A, drop sodium hydroxide solution into reaction liquid A, control the pH of reaction liquid A to be 7.3; the concentration of sodium hydroxide solution is 30%; (2) drop 295 kg of hydrocyanic acid into reaction liquid A, the drop of hydrocyanic acid is synchronous with the drop of sodium hydroxide solution, so as to continuously control the pH of the solution in the reaction kettle to be 7.3, after the drop of hydrocyanic acid is completed, use 300 Kg of desalted water to flush the pipeline, obtain reaction liquid B, continuously drop sodium hydroxide solution into reaction liquid B, control the pH of reaction liquid B to be 7.3; the drop time of hydrocyanic acid is 1.0 h; (3) use 80℃ water into the jacket to heat the reaction material, make the temperature of the reaction kettle rise to 35℃, use the diaphragm pump to punch 80 kg of the melted biological enzyme into the reaction kettle, mix uniformly, obtain reaction liquid C; slowly drop sodium hydroxide solution into reaction liquid C, continuously control the temperature of reaction liquid C to be 46℃, the pH is 7.1, so that the biological enzyme can maintain high reaction activity, when the content of 4-chloro-3-hydroxybutyric acid ethyl ester in reaction liquid C is ≤1%, the reaction is completed, obtain the crude product; Based on the yield of ethyl 4-cyano-3-hydroxybutyrate and the amount of ethyl 4-chloro-3-hydroxybutyrate added, the yield was 81.5%. The crude product contained 98.8% ethyl 4-cyano-3-hydroxybutyrate and less than 0.5% impurities.

[0037] Although the present invention has been described in detail with reference to preferred embodiments, it is not limited thereto. Various equivalent modifications or substitutions can be made to the embodiments of the present invention by those skilled in the art without departing from the spirit and essence of the invention, and such modifications or substitutions should all be within the scope of the present invention. Any variations or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention should also be covered within the protection scope of the present invention. Therefore, the protection scope of the present invention should be determined by the scope of the claims.

Claims

1. A method for synthesizing ethyl 4-cyano-3-hydroxybutyrate using pure hydrogen cyanide, characterized in that, 4-Cyano-3-hydroxybutyrate ethyl ester was synthesized using ethyl 4-chloro-3-hydroxybutyrate and hydrogen cyanide as raw materials, with a biological enzyme as a catalyst, and the pH of the reaction solution controlled between 6.5 and 7.

5. The reaction equation is as follows: 。 2. The method for synthesizing ethyl 4-cyano-3-hydroxybutyrate using pure hydrogen cyanide as described in claim 1, characterized in that, The process is as follows: (1) Add deionized water to the reaction vessel, and then add ethyl 4-chloro-3-hydroxybutyrate to obtain reaction solution A. Control the pH of reaction solution A between 6.5 and 7.

5. (2) Add hydrogen cyanide to reaction solution A to obtain reaction solution B. During the process of adding hydrogen cyanide, control the temperature of reaction solution B and continuously control the pH of reaction solution B between 6.5 and 7.

5. The time of adding hydrogen cyanide is <1.5h. (3) Adjust the temperature of reaction solution B to 35±2℃, use a diaphragm pump to pump the biological enzyme into the reaction vessel to obtain reaction solution C. Continuously control the temperature of reaction solution C between 45-48℃ and the pH between 6.9-7.1 so that the biological enzyme can maintain high reaction activity. After the reaction is completed, the crude product is obtained.

3. The method for synthesizing ethyl 4-cyano-3-hydroxybutyrate using pure hydrogen cyanide as described in claim 2, characterized in that, In step (1), sodium hydroxide solution is added dropwise to reaction solution A to adjust the pH; the volume weight ratio (L / kg) of deionized water to ethyl 4-chloro-3-hydroxybutyrate is 3.5-4.5:

1.

4. The method for synthesizing ethyl 4-cyano-3-hydroxybutyrate using pure hydrogen cyanide as described in claim 2, characterized in that, In step (2), sodium hydroxide solution is added dropwise to reaction solution B to control pH; the amount of hydrogen cyanide added is based on the amount of ethyl 4-chloro-3-hydroxybutyrate added in step (1); the weight ratio of ethyl 4-chloro-3-hydroxybutyrate to hydrogen cyanide is 10:2.9-3.

1.

5. The method for synthesizing ethyl 4-cyano-3-hydroxybutyrate using pure hydrogen cyanide as described in claim 2, characterized in that, In step (3), sodium hydroxide solution is added dropwise to reaction solution C to control the pH.

6. The method for synthesizing ethyl 4-cyano-3-hydroxybutyrate using pure hydrogen cyanide as described in claim 2, characterized in that, The crude product was extracted, centrifuged, and distilled to obtain a high-purity product.

7. The method for synthesizing ethyl 4-cyano-3-hydroxybutyrate using pure hydrogen cyanide as described in claim 2, characterized in that, The reaction system used in the method for synthesizing ethyl 4-cyano-3-hydroxybutyrate by pure hydrogen cyanide includes a reaction vessel, a sodium hydroxide dropping tank, and a biological enzyme tank; The outlet of the sodium hydroxide dripping tank is connected to the inlet A of the reaction vessel, and the outlet of the bio-enzyme tank is connected to the inlet B of the reaction vessel. A diaphragm pump is installed between the bio-enzyme tank and the reaction vessel, which transports the bio-enzymes from the bio-enzyme tank to the reaction vessel.

8. The method for synthesizing ethyl 4-cyano-3-hydroxybutyrate using pure hydrogen cyanide as described in claim 7, characterized in that, The reactor is equipped with a motor, and the output shaft of the motor is connected to a stirring paddle, the free end of which is located inside the reactor.

9. The method for synthesizing ethyl 4-cyano-3-hydroxybutyrate using pure hydrogen cyanide as described in claim 7, characterized in that, The reactor is equipped with a jacket.