High-pressure reaction device for preparing fluorine-containing medical intermediate and preparation method

Abstract

The invention discloses a high-pressure reaction device for preparing a fluorine-containing medical intermediate and a preparation method. The high-pressure reaction device comprises a kettle body, and a sampling mechanism is mounted on a top cover of the kettle body; comprising a fixed pipe and a movable rod inserted into the fixed pipe, and at least one side hole is formed in the side face of the fixed pipe; the side face of the movable rod is provided with at least one side groove, and the side wall of the fixed pipe is provided with multiple sets of pipeline holes in one-to-one correspondence with the side grooves. The lower ends of the air inlet hole and the sampling hole are provided with openings communicated with the side groove, and the upper ends of the air inlet hole and the sampling hole are respectively connected with an air inlet pipe and a sampling pipe; a pump body is mounted on the top cover, the sampling pipe is connected with a liquid inlet of the pump body, and the air inlet pipe is connected with an air inlet of the pump body; the outer end of the movable rod is connected with a driving unit for driving the movable rod to rotate or twitch, and the driving unit switches the side groove between the opening position and the side hole position. According to the high-pressure reaction device and the preparation method, multi-layer simultaneous sampling can be carried out on the kettle body, and the reaction degree can be better judged conveniently.

Description

Technical Field

[0001] The present invention relates to the field of high-pressure reaction equipment, and in particular to a high-pressure reaction device and a preparation method for preparing fluorine-containing pharmaceutical intermediates. Background Art

[0002] The preparation of fluorinated pharmaceutical intermediates requires specialized high-pressure reactors, where precise control of reaction conditions ensures product purity and quality. For example, if the reaction is performed in a high-temperature, high-pressure reactor, the reactants must be sampled and analyzed throughout the reaction.

[0003] Patent CN218546260U discloses a sampling device for a reactor, including a reactor body and a mixing assembly installed at the center of the reactor body, a feed pipe connected to one side of the top of the reactor body, and a discharge pipe connected to the bottom of one side of the reactor body, the bottom outer wall of the reactor body is installed with equidistantly distributed support legs, and a sampling structure is installed on one side of the top of the reactor body; the sampling structure includes a sampling tube installed in the reactor body, strip holes opened on both sides of the sampling tube and located inside the reactor body, and a sampling screw rotatably connected to the center of the inner wall of the sampling tube.

[0004] The sampling mechanism used in this reactor sampling device cannot perform simultaneous layered sampling. The layered sampling is time-delayed, resulting in significant sampling deviations and impacting detection accuracy. Furthermore, the sampling mechanism utilizes a sampling screw, which takes samples directly within the reactor body. The pressure within the reactor significantly impacts sampling, posing a significant safety hazard. Summary of the Invention

[0005] The purpose of the present invention is to provide a high-pressure reaction device and preparation method for preparing fluorine-containing pharmaceutical intermediates. The high-pressure reaction device and preparation method can simultaneously sample multiple layers of the kettle body, thereby facilitating a better judgment of the reaction degree.

[0006] In order to achieve the above-mentioned object, the present invention provides a high-pressure reaction device for preparing fluorine-containing pharmaceutical intermediates, the high-pressure reaction device comprising a kettle body, a sampling mechanism installed on the top cover of the kettle body; the sampling mechanism comprises a fixed tube and a movable rod inserted into the fixed tube, the side of the fixed tube is provided with at least one side hole; the side of the movable rod is provided with at least one side groove corresponding to the side hole, and the side wall of the fixed tube is provided with multiple groups of pipe holes corresponding to the side grooves one by one; the pipe holes include an air inlet hole and a sampling hole, the lower ends of the air inlet hole and the sampling hole are provided with openings communicating with the side grooves, and the upper ends are respectively connected to the air inlet pipe and the sampling tube; a pump body is installed on the top cover, the sampling tube is connected to the liquid inlet of the pump body, and the air inlet pipe is connected to the air inlet of the pump body; the outer end of the movable rod is connected to a driving unit for driving it to rotate or pump, and the driving unit switches the side groove between the opening position and the side hole position.

[0007] Preferably, the driving unit includes columns symmetrically arranged on both sides of the fixed tube, the upper ends of the columns are provided with studs, the studs are sequentially sleeved with mounting plates and nuts, a cylinder or motor is installed on the mounting plate, and the shaft of the cylinder or motor is connected to the movable rod.

[0008] Preferably, a guide tube coaxial with the fixing tube is provided on the top cover, and the fixing tube is detachably inserted into the guide tube and connected to the guide tube via a flange.

[0009] Preferably, a sampling interface nozzle and an air intake interface nozzle are provided on the pump body.

[0010] Preferably, a motor frame is provided at the top end of the top cover, a stirring motor is mounted on the motor frame, and a shaft of the stirring motor extends into the kettle body and is provided with stirring blades.

[0011] Preferably, the stirring blades are provided with 3-5 pieces of co-directional spirals.

[0012] Preferably, the pump body is mounted on the top cover via a pump frame.

[0013] Preferably, a feeding port is provided on the top cover at a side opposite to the fixed pipe, and a discharge port and a sewage outlet are provided at the bottom end of the kettle body.

[0014] Preferably, the inner lining of the kettle is made of polytetrafluoroethylene.

[0015] The present invention also provides a preparation method for preparing fluorine-containing pharmaceutical intermediates, which uses the high-pressure reaction device; the preparation method includes adding raw materials into a kettle according to a predetermined ratio for reaction, and sampling and analyzing reactants at different depths during the reaction.

[0016] According to the above technical solution, the high-pressure reaction device for preparing fluorine-containing pharmaceutical intermediates in the present invention has the following beneficial effects: 1. The sampling mechanism can simultaneously sample the reactants in the kettle body in layers, specifically by driving the movable rod to rotate or pull by the driving unit, so that each side groove is connected to the corresponding side hole, so that the nearby reactants can naturally flow into and fill the side groove. When sampling, the side groove is separated from the side hole and connected to the opening by rotating or pulling the movable rod. Each side groove corresponds to two openings. By starting the pump body, the opening connected to the sampling hole enters the reactants and is extracted. In order to maintain the pressure balance in the side groove, the opening connected to the air inlet hole flows into new gas, which can be nitrogen, without affecting the normal progress of the reaction. Since multiple side grooves can be sampled simultaneously by the movement of the movable rod, more accurate sampling and analysis data can be obtained. 2. Since each sampling only extracts the reactants in the side groove and does not directly extract the reactor in the kettle body, the influence of the high pressure in the kettle body on the extraction process can be reduced.

[0017] Other features and advantages of the present invention will be described in detail in the following detailed description. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] The accompanying drawings are used to provide a further understanding of the present invention and constitute a part of the specification. Together with the following detailed description, they are used to explain the present invention but do not constitute a limitation of the present invention. In the accompanying drawings:

[0019] Figure 1 This is a schematic diagram of the overall structure of a preferred embodiment of a high-pressure reaction device;

[0020] Figure 2 This is a schematic top view of a preferred embodiment of a high-pressure reaction device;

[0021] Figure 3 yes Figure 2 AA cross-sectional structural diagram;

[0022] Figure 4 yes Figure 3 Schematic diagram of the local enlarged structure of area B in the middle;

[0023] Figure 5 It is a schematic diagram of the overall structure of a preferred embodiment of the fixed tube;

[0024] Figure 6 1 is a schematic top view of a preferred embodiment of a fixed tube;

[0025] Figure 7 yes Figure 6 Schematic diagram of CC cross-section structure;

[0026] Figure 8 yes Figure 7 Schematic diagram of the locally enlarged structure of area D in the middle.

[0027] Description of Reference Numerals

[0028] 1- kettle body; 2- top cover; 3- feeding port; 4- discharging port; 5- guide tube; 6- drain outlet; 7- column; 8- nut; 9- mounting plate; 10- cylinder or motor; 11- motor frame; 12- stirring motor; 13- shaft; 14- pump body; 15- sampling interface nozzle; 16- air inlet interface nozzle; 17- pump frame; 18- air inlet pipe; 19- sampling tube; 20- stirring blade; 21- fixed tube; 22- movable rod; 23- side groove; 24- pipe hole; 25- side hole; 26- flange; 27- opening. DETAILED DESCRIPTION

[0029] The following is a detailed description of the specific embodiments of the present invention in conjunction with the accompanying drawings. It should be understood that the specific embodiments described herein are only used to illustrate and explain the present invention and are not intended to limit the present invention.

[0030] In the present invention, unless otherwise stated, directional words contained in terms such as "up, down, left, right, front, back, inside, outside" merely represent the orientation of the term in normal usage, or are common names understood by those skilled in the art, and should not be regarded as limitations on the term.

[0031] See also Figure 1-8 The high-pressure reaction device for preparing fluorine-containing pharmaceutical intermediates shown in the figure comprises a kettle body 1, a sampling mechanism is installed on the top cover 2 of the kettle body 1; the sampling mechanism comprises a fixed tube 21 and a movable rod 22 inserted into the fixed tube 21, the side of the fixed tube 21 is provided with at least one side hole 25; the side of the movable rod 22 is provided with at least one side groove 23 corresponding to the side hole 25, and the side wall of the fixed tube 21 is provided with multiple groups of pipe holes 24 corresponding to the side grooves 23; The pipe hole 24 includes an air inlet hole and a sampling hole. The lower ends of the air inlet hole and the sampling hole are provided with an opening 27 connected to the side groove 23, and the upper ends are respectively connected to the air inlet pipe 18 and the sampling tube 19; the pump body 14 is installed on the top cover 2, the sampling tube 19 is connected to the liquid inlet of the pump body 14, and the air inlet pipe 18 is connected to the air inlet of the pump body 14; the outer end of the movable rod 22 is connected to a driving unit that drives it to rotate or pull, and the driving unit switches the side groove 23 between the position of the opening 27 and the position of the side hole 25.

[0032] Through the implementation of the above technical solution, the sampling mechanism provided can simultaneously sample the reactants in the kettle body 1 in layers. The specific method is: the driving unit drives the movable rod 22 to rotate or pull, so that each side groove 23 is connected to the corresponding side hole 25, so that the nearby reactants can naturally flow into and fill the side groove 23. When sampling, by rotating or pulling the movable rod 22, the side groove 23 is separated from the side hole 25 and connected to the opening 27. Each side groove 23 corresponds to two openings 27, and the side groove 23 is connected to the two openings 27. By starting the pump body 14, the reactants enter the opening 27 connected to the sampling hole and are extracted. In order to maintain the pressure balance in the side groove 23, new gas flows into the opening 27 connected to the air inlet hole. The gas can be nitrogen and does not affect the normal progress of the reaction. Since multiple side grooves 23 can be sampled simultaneously through the movement of the movable rod 22, more accurate sampling and analysis data can be obtained. Since each sampling only extracts the reactants in the side groove 23 and does not directly extract the reactor in the kettle body 1, the influence of the high pressure in the kettle body 1 on the extraction process can be reduced.

[0033] In the drawings of the present invention, a side groove 23, a side hole 25, and a group of pipe holes 24 are provided as an example. When multiple groups of such a combination are provided, the side holes 25 are arranged in a vertically staggered manner, so that each group of pipe holes 24 can be staggered and distributed, resulting in a more reasonable arrangement. Correspondingly, a corresponding number of liquid inlets and air inlets are also provided on the pump body 14.

[0034] In this embodiment, a drive unit is further provided, comprising upright posts 7 symmetrically disposed on both sides of the fixed tube 21. Studs are disposed at the upper ends of the upright posts 7, which are sequentially sleeved with mounting plates 9 and nuts 8. A cylinder or motor 10 is mounted on the mounting plate 9, and the shaft of the cylinder or motor 10 is connected to the movable rod 22. This arrangement facilitates disassembly of the drive unit. After removing the nuts 8, the mounting plate 9 can be further removed, thereby facilitating removal of the movable rod 22.

[0035] In this embodiment, the top cover 2 is provided with a guide tube 5 coaxial with the fixing tube 21. The fixing tube 21 is removably inserted into the guide tube 5 and connected to the guide tube 5 via a flange 26. This arrangement facilitates removal of the fixing tube 21, and the guide tube 5 serves as a guide and positioning device during installation. Guide ribs may also be provided between the guide tube 5 and the wall of the fixing tube 21 to facilitate installation and alignment.

[0036] In this embodiment, the pump body 14 is provided with a sampling interface nozzle 15 and an air inlet interface nozzle 16. The sampling interface nozzle 15 can be used to receive the sample drawn out for sampling, and the air inlet interface nozzle 16 is connected to a nitrogen source to replenish nitrogen into the side tank 23 to balance the pressure in the side tank 23.

[0037] In this embodiment, a motor frame 11 is provided at the top of the top cover 2, and a stirring motor 12 is mounted on the motor frame 11. The shaft 13 of the stirring motor 12 extends into the kettle body 1 and is provided with a stirring blade 20. Through such a configuration, the stirring motor 12 drives the stirring blade 20 to rotate and stir the reactants.

[0038] In this embodiment, in order to further provide a layout of the stirring blades 20, the stirring blades 20 are provided with 3-5 blades spiraling in the same direction. The shape of the stirring blades 20 is not limited to a flat shape, and can be spiral, hollow or comb-shaped.

[0039] In this embodiment, the pump body 14 is mounted on the top cover 2 via a pump frame 17. The pump body 14 and the pump frame 17 can be connected by bolts for easy disassembly.

[0040] In this embodiment, a feeding port 3 is provided on the top cover 2 at a side opposite to the fixed pipe 21 , and a discharge port 4 and a sewage outlet 6 are provided at the bottom end of the kettle body 1 .

[0041] In this embodiment, considering that the fluorine-containing pharmaceutical intermediate preparation process is highly corrosive to metal and glass liners, the inner lining of the kettle body 1 is made of polytetrafluoroethylene.

[0042] The present invention further provides a method for preparing a fluorine-containing pharmaceutical intermediate, using the high-pressure reaction apparatus described above. The method comprises adding raw materials in a predetermined proportion to a kettle 1 for reaction, and simultaneously sampling and analyzing the reactants at different depths during the reaction. This sampling method provides a more accurate sample.

[0043] The preferred embodiments of the present invention are described in detail above in conjunction with the accompanying drawings. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the scope of protection of the present invention.

[0044] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any appropriate manner without contradiction. In order to avoid unnecessary repetition, the present invention will not further describe various possible combinations.

[0045] In addition, the various embodiments of the present invention may be arbitrarily combined, and as long as they do not violate the concept of the present invention, they should also be regarded as the contents disclosed by the present invention.

Claims

1. A high-pressure reaction device for preparing fluorine-containing pharmaceutical intermediates, characterized in that: The high-pressure reaction device comprises a kettle body (1), and a sampling mechanism is installed on the top cover (2) of the kettle body (1); The sampling mechanism comprises a fixed tube (21) and a movable rod (22) inserted into the fixed tube (21), and at least one side hole (25) is provided on a side surface of the fixed tube (21); The side surface of the movable rod (22) is provided with at least one side groove (23) corresponding to the side hole (25), and the side wall of the fixed tube (21) is provided with multiple groups of pipe holes (24) corresponding one-to-one to the side grooves (23); The pipeline hole (24) includes an air inlet hole and a sampling hole, the lower ends of the air inlet hole and the sampling hole are provided with an opening (27) communicating with the side groove (23), and the upper ends are connected to the air inlet pipe (18) and the sampling pipe (19) respectively; A pump body (14) is mounted on the top cover (2), the sampling tube (19) is connected to the liquid inlet of the pump body (14), and the air inlet pipe (18) is connected to the air inlet of the pump body (14); The outer end of the movable rod (22) is connected to a driving unit for driving it to rotate or move, and the driving unit switches the side groove (23) between the opening (27) position and the side hole (25) position.

2. The high-pressure reaction device for preparing fluorine-containing pharmaceutical intermediates according to claim 1, characterized in that: The driving unit comprises columns (7) symmetrically arranged on both sides of the fixed tube (21), the upper ends of the columns (7) are provided with studs, the studs are sequentially sleeved with mounting plates (9) and nuts (8), the mounting plates (9) are mounted with cylinders or motors (10), and the shafts of the cylinders or motors (10) are connected to the movable rods (22).

3. The high-pressure reaction device for preparing fluorine-containing pharmaceutical intermediates according to claim 1, characterized in that: The top cover (2) is provided with a guide tube (5) coaxial with the fixed tube (21); the fixed tube (21) is detachably inserted into the guide tube (5) and connected to the guide tube (5) via a flange (26).

4. The high-pressure reaction device for preparing fluorine-containing pharmaceutical intermediates according to claim 1, characterized in that: The pump body (14) is provided with a sampling interface nozzle (15) and an air intake interface nozzle (16).

5. The high-pressure reaction device for preparing fluorine-containing pharmaceutical intermediates according to claim 1, characterized in that: A motor frame (11) is provided at the top end of the top cover (2), a stirring motor (12) is mounted on the motor frame (11), a shaft (13) of the stirring motor (12) extends into the kettle body (1) and is provided with a stirring blade (20).

6. The high-pressure reaction device for preparing fluorine-containing pharmaceutical intermediates according to claim 5, characterized in that: The stirring blades (20) are provided with 3-5 pieces of spirals in the same direction.

7. The high-pressure reaction device for preparing fluorine-containing pharmaceutical intermediates according to claim 1, characterized in that: The pump body (14) is mounted on the top cover (2) via a pump frame (17).

8. The high-pressure reaction device for preparing fluorine-containing pharmaceutical intermediates according to claim 1, characterized in that: A feeding port (3) is provided on the top cover (2) at a side opposite to the fixed pipe (21), and a discharge port (4) and a sewage outlet (6) are provided at the bottom end of the kettle body (1).

9. The high-pressure reaction device for preparing fluorine-containing pharmaceutical intermediates according to claim 1, characterized in that: The inner lining of the kettle body (1) is made of polytetrafluoroethylene.

10. A method for preparing a fluorine-containing pharmaceutical intermediate, characterized in that: The preparation method uses the high-pressure reaction device according to any one of claims 1 to 9; The preparation method comprises the steps of feeding raw materials into a kettle (1) in a predetermined ratio to carry out a reaction, and sampling and analyzing reactants at different depths during the reaction.

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