Hydrogenation synthesis system for (2S, 3R)-2-benzoylaminomethyl-3-hydroxybutyrate

Through the full-process nitrogen replacement and distribution control system, safety hazards and cost problems in the hydrogenation synthesis process are solved, and safe and efficient utilization of hydrogen resources is achieved.

CN223209452UActive Publication Date: 2025-08-12PINGSHAN INST OF BIOMEDICINE SOUTHERN UNIV OF SCI & TECH +1
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Patent Information

Application Number
CN202422471913.3
Authority / Receiving Office
CN · China
Patent Type
Utility models(China)
Current Assignee / Owner
Filing Date
2024-10-14
Publication Date
2025-08-12
Estimated Expiration
2034-10-14

AI Technical Summary

Technical Problem

During the hydrogenation process of the synthetic (2S,3R)-2-benzolamidine-3-hydroxybutyrate, hydrogen becomes an uncertain factor in production safety, and the existing equipment and processes may bring dangers and are costly.

Method used

The full-process nitrogen replacement and distribution control system is adopted to replace the system through nitrogen to ensure the inert and positive pressure atmosphere of the system, and to separate nitrogen and hydrogen by using a gas separation device to achieve resource reuse and reduce risks and costs.

Benefits of technology

Improve production safety, reduce risk factors, and reduce costs through resource reuse.

✦ Generated by Eureka AI based on patent content.

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Abstract

The utility model relates to the technical field of chemistry and chemical engineering, and particularly discloses a (2S, 3R)-2-benzoylaminomethyl-3-hydroxybutyrate synthesis system which comprises a micro-channel reaction pipeline, and a feed port of the micro-channel reaction pipeline is connected with a discharge port of a dissolving kettle and an output pipe of a nitrogen tank and an output pipe of a hydrogen tank; a discharge port of the micro-channel reaction pipeline is connected with a feed port of the concentration crystallization tank, the feed port of the concentration crystallization tank is also connected with discharge ports of the saturated salt water tank and the recovered solvent tank, the discharge port of the concentration crystallization tank is connected with a feed port of the recovered solvent storage tank, and a heat exchange coil pipe is arranged in the concentration crystallization tank. According to the (2S, 3R)-2-benzoylaminomethyl-3-hydroxybutyrate system provided by the utility model, in a hydrogenation process, the whole process of filling the whole system with nitrogen is realized, for example, before hydrogen is introduced into a micro-channel reaction pipeline, the pipeline is replaced with the nitrogen, so that the production safety coefficient is increased.
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Description

Technical Field

[0001] The utility model relates to the technical field of chemistry and chemical engineering, in particular to the technical field of drug synthesis, and discloses a (2S, 3R)-2-benzamidomethyl-3-hydroxybutyrate synthesis system. Background Art

[0002] (2S, 3R)-2-Benzamidomethyl-3-hydroxybutyrate is an important intermediate in the synthesis of carbapenem antibiotics. The synthesis method of this compound is as follows:

[0003]

[0004] During the synthesis process, asymmetric hydrogenation is required. During the hydrogenation process or in the refining step after hydrogenation, hydrogen often becomes a safety uncertainty factor in industrial production. Inappropriate equipment and technology may bring danger. Utility Model Content

[0005] Based on the above-mentioned deficiencies in the prior art, the present invention aims to provide a safe hydrogenation synthesis system for (2S, 3R)-2-benzamidomethyl-3-hydroxybutyrate, which can effectively save costs and reduce the risk factor.

[0006] The first aspect of the present invention provides a hydrogenation synthesis system for (2S, 3R)-2-benzamidomethyl-3-hydroxybutyrate, comprising a microchannel reaction pipeline, wherein the feed port of the microchannel reaction pipeline (7) is connected to the discharge port of the reaction material dissolving kettle (3), the output pipe of the nitrogen tank (2) and the hydrogen tank (1);

[0007] The discharge port of the microchannel reaction pipeline (7) is connected to the feed port of the concentration crystallization kettle (13);

[0008] The feed port of the concentration crystallization kettle (13) is also connected to the discharge ports of the saturated brine tank (12) and the recrystallization solvent tank (9);

[0009] The discharge port of the concentration crystallization kettle (13) is connected to the feed port of the recovery solvent storage tank (15);

[0010] The concentration crystallization kettle (13) is provided with a heat exchange coil, and the heat exchange coil includes a heating coil and a cooling coil.

[0011] In some specific embodiments of the first aspect of the present invention, a condenser (14) is further provided on the pipeline connecting the discharge port of the concentration crystallization kettle (13) and the feed port of the recovery solvent storage tank (15).

[0012] In some specific embodiments of the first aspect of the present invention, the output pipes of the reaction material dissolving kettle (3), the nitrogen tank (2) and the hydrogen tank (1) are all provided with electromagnetic valves (28), and the electromagnetic valves (28) are used to control the nitrogen tank (2) and the hydrogen tank (1) to deliver gas to the microchannel reaction pipeline (7).

[0013] In some specific embodiments of the first aspect of the present invention, the electromagnetic valve (28) is electrically connected to a distributed control system.

[0014] In some specific embodiments of the first aspect of the present invention, the concentration crystallization kettle (13) is also connected to the inlet of the mixed gas buffer tank (17), the outlet of the mixed gas buffer tank (17) is connected to the inlet of the gas separation device (19), the hydrogen outlet of the gas separation device (19) is connected to the inlet of the hydrogen tank (1), and the nitrogen outlet of the gas separation device (19) is connected to the inlet of the nitrogen tank (2).

[0015] In some specific embodiments of the first aspect of the present invention, a gas flow meter (4) is installed at the outlet of the nitrogen tank (2) and the hydrogen tank (1).

[0016] In some specific embodiments of the first aspect of the present invention, the nitrogen tank (2) output pipe is connected to the reaction material dissolving kettle (3), the recrystallization solvent tank (9), the reaction solvent storage tank (15), and the aqueous phase storage tank (16).

[0017] In some specific embodiments of the first aspect of the present invention, the hydrogen tank (1), the nitrogen tank (2), the reaction material dissolving kettle (3), the recrystallization solvent tank (9), the saturated brine tank (12), the concentration crystallization kettle (13), the reaction solvent storage tank (15), the aqueous phase storage tank (16), and the mixed gas buffer tank (17) are provided with safety devices, and the safety devices are selected from bursting discs and safety valves.

[0018] In some specific embodiments of the first aspect of the present invention, the material of the microchannel reaction pipeline (7) is selected from polytetrafluoroethylene, 316 steel or titanium alloy steel.

[0019] In some specific embodiments of the first aspect of the present invention, the hydrogen tank (1), the nitrogen tank (2), the reaction material dissolving kettle (3), the recrystallization solvent tank (9), the saturated brine tank (12), the concentration crystallization kettle (13), the reaction solvent storage tank (15), the aqueous phase storage tank (16), and the mixed gas buffer tank (17) are made of a material selected from 316 steel or titanium alloy steel.

[0020] Advantages of this utility model:

[0021] The (2S, 3R)-2-benzamidomethyl-3-hydroxybutyrate system provided by the present invention achieves full filling of the entire system with nitrogen during the hydrogenation process. For example, before hydrogen is introduced into the microchannel reaction pipeline, the pipeline is first replaced with nitrogen, thereby increasing the production safety factor. In some optional specific embodiments, a distributed control system is used to control the nitrogen, hydrogen, and dissolution kettle outlet solenoid valves to avoid manual operation errors. In some optional specific embodiments, a nitrogen tank is connected to each reaction storage tank and the upper part of the dissolution kettle to maintain the inertness and positive pressure atmosphere of each container, further improving the safety factor. In some optional specific embodiments, a gas separation device, such as an air separation tower or a pressure swing adsorption device, is also used to separate the nitrogen and hydrogen mixed gas from the concentration crystallization kettle, and the gas resources are reused and recovered, thereby reducing costs. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 The first process flow chart of the utility model is shown;

[0023] Figure 2 The second process flow diagram of the utility model is shown;

[0024] 1. Hydrogen tank; 2. Nitrogen tank; 3. Reaction material dissolving kettle; 4. Gas flowmeter; 7. Microchannel reaction pipeline; 9. Recrystallization solvent tank; 10. Recrystallization solvent pump; 11. Saturated brine pump; 12. Saturated brine tank; 13. Concentration crystallization kettle; 14. Condenser; 15. Recovery solvent storage tank; 16. Water phase storage tank; 17. Mixed gas buffer tank; 19. Gas separation device; 191. PSA-H2 adsorption device; 20. Compressor; 21. Electric control line; 22. Water phase liquid pump; 23. Reaction solvent pump; 24. Hydrogen valve; 25. Nitrogen valve; 26. Microchannel pipeline feed valve; 27. Microchannel pipeline discharge valve; 28. Solenoid valve; 171. Drain pipe. DETAILED DESCRIPTION

[0025] In order to make those skilled in the art better understand the present invention, the present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments.

[0026] See also Figure 1 The present invention specifically discloses a hydrogenation synthesis system for (2S, 3R)-2-benzamidomethyl-3-hydroxybutyrate, comprising a microchannel reaction pipeline 7, wherein the feed port of the microchannel reaction pipeline 7 is connected to the discharge port of the reaction material dissolving kettle 3, the nitrogen tank 2, and the output pipe of the hydrogen tank 1;

[0027] The discharge port of the microchannel reaction pipeline 7 is connected to the feed port of the concentration crystallization kettle 13;

[0028] The feed port of the concentration crystallization kettle 13 is also connected to the discharge port of the saturated brine tank 12 and the recrystallization solvent tank 9;

[0029] The discharge port of the concentration crystallization kettle 13 is connected to the feed port of the recovery solvent storage tank 15;

[0030] The concentration crystallization kettle 13 is provided with a heat exchange coil, which includes a heating coil and a cooling coil.

[0031] The output pipes of the reaction material dissolving kettle 33 , the nitrogen tank 2 and the hydrogen tank 1 are all provided with electromagnetic valves 28 , and the electromagnetic valves 28 are used to control the nitrogen tank 2 and the hydrogen tank 1 to deliver gas to the microchannel reaction pipeline 7 .

[0032] The electromagnetic valve 28 provided on the output tank of the reaction material dissolving kettle 33 is the microchannel pipeline feed valve 26, the electromagnetic valve 28 provided on the output pipe of the hydrogen tank 1 is the hydrogen valve 24, and the electromagnetic valve 28 provided on the output pipe of the nitrogen tank 2 is the nitrogen valve 25.

[0033] When in use, the substrate 2-(benzamidomethyl)-3-oxobutanoic acid methyl ester (CAS: 129994-60-1), dichloro(cymene)ruthenium(II) dimer ([Ru(p-cemene)Cl2]2, one of the additives L1 to L4, and dichloromethane-ethanol (V:V=1:1) are added to the reaction material dissolving kettle 3 for dissolution. First, the hydrogen valve 24 and the microchannel pipeline feed valve 26 are closed, the nitrogen valve 25 is opened, and the pipeline is replaced with nitrogen to ensure that there is no air in the microchannel pipeline. Then, the microchannel pipeline feed valve 26 is opened, and the material in the reaction material dissolving kettle 3 is pumped into according to the carrying capacity of the microchannel reaction pipeline 7. The hydrogen valve 24 is opened to introduce hydrogen into the microchannel pipeline, and the microchannel pipeline discharge valve 27 is closed to react.

[0034]

[0035] After the reaction is completed, the microchannel pipeline discharge valve 27 is opened, the hydrogen valve 24 is closed, and the nitrogen valve 25 is opened to pump the crude material in the microchannel pipeline into the concentration crystallization kettle 13. The excess hydrogen enters the mixed gas buffer tank 17 through the pipeline above the concentration crystallization kettle 13.

[0036] First, the material in the concentration crystallization kettle 13 is heated using a heat coil and vacuumed at the same time to recover the solvent in the concentration crystallization kettle 13 . The recovered solvent passes through the condenser 14 and returns to the recovery solvent storage tank 15 .

[0037] After the solvent is recovered, the recrystallization solvent pump 10 is used to pump the recrystallization solvent, such as n-heptane, from the recrystallization solvent tank 9 into the concentration crystallization kettle 13 and heat to dissolve.

[0038] Brine is pumped from the saturated brine tank 12 into the concentration crystallization kettle 13 through the saturated brine pump 11. The brine includes but is not limited to saturated sodium sulfate and saturated sodium chloride. After washing and phase separation, the aqueous phase enters the aqueous phase storage tank 16 through the bottom valve.

[0039] The concentration crystallization kettle 13 was cooled using a cooling coil, and (2S, 3R)-2-benzamidomethyl-3-hydroxybutyrate (CAS: 124044-13-9) was obtained by crystallization.

[0040] In some optional embodiments, a gas flow meter 4 is installed at the outlet of the nitrogen tank 2 and the hydrogen tank 1 .

[0041] In some optional embodiments, the solenoid valve 28 is electrically connected to a distributed control system via an electric control line 21 .

[0042] In some optional embodiments, an exhaust pipe 171 is provided above the mixed gas buffer tank 17 , and the nitrogen-hydrogen mixed gas containing a small amount of hydrogen in the mixed gas buffer tank 17 is discharged through the exhaust pipe 171 .

[0043] Alternatively, the hydrogen and nitrogen mixed gas in the mixed gas buffer tank 17 is not discharged through the exhaust pipe 171, such as Figure 2 As shown, the concentration crystallization kettle 13 is also connected to the inlet of the mixed gas buffer tank 17, the outlet of the mixed gas buffer tank 17 is connected to the inlet of the gas separation device 19, the hydrogen outlet of the gas separation device 19 is connected to the inlet of the hydrogen tank 1, and the nitrogen outlet of the gas separation device 19 is connected to the inlet of the nitrogen tank 2.

[0044] Preferably, the gas separation device 19 is an air separation tower. After separation in the air separation tower and then pressure reduction by a pressure reducing valve, the hydrogen and nitrogen in the mixed gas buffer tank 17 enter the hydrogen tank 1 and the nitrogen tank 2 respectively.

[0045] Or, preferably, Figure 2 As shown, the gas separation device 19 is a PSA-H2 adsorption device 191, which includes a pair of packed towers filled with molecular sieves and a compressor 20. The safety requirements of the pressure swing adsorption PSA device refer to GB / T 42857-2023.

[0046] In some optional embodiments, the output pipe of the nitrogen tank 2 is connected to the reaction material dissolution kettle 33, the recrystallization solvent tank 9, the recovery solvent storage tank 15, and the water phase storage tank 16.

[0047] In some optional embodiments, the hydrogen tank 1, nitrogen tank 2, reaction material dissolution kettle 33, recrystallization solvent tank 9, saturated brine tank 12, concentration crystallization kettle 13, recovery solvent storage tank 15, aqueous phase storage tank 16, and mixed gas buffer tank 17 are provided with safety devices, and the safety devices are selected from bursting discs and safety valves.

[0048] In some optional embodiments, the material of the microchannel reaction pipeline 7 is selected from polytetrafluoroethylene, 316 steel and titanium alloy steel.

[0049] In some optional embodiments, the hydrogen tank 1, the nitrogen tank 2, the reaction material dissolution kettle 33, the recrystallization solvent tank 9, the saturated brine tank 12, the concentration crystallization kettle 13, the recovery solvent storage tank 15, the aqueous phase storage tank 16, and the mixed gas buffer tank 17 are made of materials selected from 316 steel and titanium alloy steel.

[0050] The above-described embodiments are only used to illustrate the technical solutions of the present application, rather than to limit them. Although the present application has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. These modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the various embodiments of the present application, and should all be included in the scope of protection of the present application.

Claims

1. A hydrogenation synthesis system for (2S, 3R)-2-benzamidomethyl-3-hydroxybutyrate, characterized in that: It comprises a microchannel reaction pipeline, wherein the feed port of the microchannel reaction pipeline (7) is connected to the discharge port of the reaction material dissolving kettle (3), the output pipes of the nitrogen tank (2) and the hydrogen tank (1); The discharge port of the microchannel reaction pipeline (7) is connected to the feed port of the concentration crystallization kettle (13); The feed port of the concentration crystallization kettle (13) is also connected to the discharge ports of the saturated brine tank (12) and the recrystallization solvent tank (9); The discharge port of the concentration crystallization kettle (13) is connected to the feed port of the recovery solvent storage tank (15); The concentration crystallization kettle (13) is provided with a heat exchange coil, and the heat exchange coil includes a heating coil and a cooling coil.

2. The hydrogenation synthesis system for (2S, 3R)-2-benzamidomethyl-3-hydroxybutyrate according to claim 1, characterized in that: A condenser (14) is also provided on the pipeline connecting the discharge port of the concentration crystallization kettle (13) and the feed port of the recovery solvent storage tank (15).

3. The hydrogenation synthesis system for (2S, 3R)-2-benzamidomethyl-3-hydroxybutyrate according to claim 1, characterized in that: The output pipes of the reaction material dissolving kettle (3), the nitrogen tank (2) and the hydrogen tank (1) are all provided with electromagnetic valves (28), and the electromagnetic valves (28) are used to control the nitrogen tank (2) and the hydrogen tank (1) to deliver gas to the microchannel reaction pipeline (7).

4. The hydrogenation synthesis system for (2S, 3R)-2-benzamidomethyl-3-hydroxybutyrate according to claim 3, characterized in that: The electromagnetic valve (28) is electrically connected to the distributed control system.

5. The hydrogenation synthesis system of (2S, 3R)-2-benzamidomethyl-3-hydroxybutyrate according to claim 1, characterized in that: The concentration crystallization kettle (13) is also connected to the inlet of the mixed gas buffer tank (17), the outlet of the mixed gas buffer tank (17) is connected to the inlet of the gas separation device (19), the hydrogen outlet of the gas separation device (19) is connected to the inlet of the hydrogen tank (1), and the nitrogen outlet of the gas separation device (19) is connected to the inlet of the nitrogen tank (2).

6. The hydrogenation synthesis system for (2S, 3R)-2-benzamidomethyl-3-hydroxybutyrate according to claim 1, characterized in that: Gas flow meters (4) are installed at the outlets of the nitrogen tank (2) and the hydrogen tank (1).

7. The hydrogenation synthesis system for (2S, 3R)-2-benzamidomethyl-3-hydroxybutyrate according to claim 1, characterized in that: The nitrogen tank (2) output pipe is connected to the reaction material dissolving kettle (3), the recrystallization solvent tank (9), the reaction solvent storage tank (15), and the water phase storage tank (16).

8. The hydrogenation synthesis system for (2S, 3R)-2-benzamidomethyl-3-hydroxybutyrate according to claim 1, characterized in that: The hydrogen tank (1), nitrogen tank (2), reaction material dissolving kettle (3), recrystallization solvent tank (9), saturated brine tank (12), concentration crystallization kettle (13), reaction solvent storage tank (15), aqueous phase storage tank (16), and mixed gas buffer tank (17) are provided with safety devices, and the safety devices are selected from bursting discs and safety valves.

9. The hydrogenation synthesis system for (2S, 3R)-2-benzamidomethyl-3-hydroxybutyrate according to claim 1, characterized in that: The material of the microchannel reaction pipeline (7) is selected from polytetrafluoroethylene, 316 steel or titanium alloy steel.

10. The system for synthesizing (2S, 3R)-2-benzamidomethyl-3-hydroxybutyrate by hydrogenation according to any one of claims 1 to 9, characterized in that: The hydrogen tank (1), the nitrogen tank (2), the reaction material dissolving kettle (3), the recrystallization solvent tank (9), the saturated brine tank (12), the concentration crystallization kettle (13), the reaction solvent storage tank (15), the aqueous phase storage tank (16), and the mixed gas buffer tank (17) are made of materials selected from 316 steel or titanium alloy steel.