Solid-phase synthesis device

Abstract

The utility model belongs to the technical field of solid-phase synthesis, and particularly relates to a solid-phase synthesis device which comprises a liquid conveying device, a gas conduit, a piston assembly, a reaction tank, a sampling emptying device, a rotating shaft device, a lower end cover, a waste liquid tank, a temperature control jacket and a conveying pipeline. The device has the beneficial effects that the reaction tank and a solid-phase carrier are cleaned in a flowing liquid manner, so that the use of a solvent is greatly reduced, and the whole solid-phase synthesis solvent can be reduced by two thirds; in the reaction process, the volume in the reaction tank is larger than or equal to the volume of reaction liquid, and the solid-phase carrier moves along with the reaction tank in a swinging state, so that the problem of non-uniform reaction is effectively solved; oxygen and moisture in the air are isolated, closed reaction is realized, and side reaction is effectively avoided; the problem that a traditional reaction kettle and a continuous flow synthesis process are difficult to sample is solved.

Description

Technical Field

[0001] The present invention relates to the field of practical solid phase synthesis technology, and particularly to a solid phase synthesis device. Background Art

[0002] At present, the solid phase synthesis device mostly adopts double-layer glass reactor, and a filter device made of PTFE material is connected to the bottom, which is connected to the reactor body by a flange. In order to ensure uniform reaction, stirring is mostly adopted. After the reaction, the reaction solvent is removed by suction filtration or pump, and the solid phase carrier is left in the reactor. By adding a large amount of solvent for washing multiple times, it is ensured that the material of the previous step reaction is completely removed. However, each time washing, a large amount of solvent is required, which will lead to increased costs and is unfriendly to the environment. Therefore, it is a topic that urgently needs to be studied by improving the solid phase synthesis device to reduce the excessive use of solvents. Utility Model Content

[0003] In view of this, in order to overcome the deficiencies of the prior art, the utility model provides a solid phase synthesis device, which greatly reduces excessive use of solvents while improving uniform solid-liquid phase reaction, reduces costs and improves efficiency.

[0004] In order to achieve the above purpose, the utility model adopts the following technical solutions:

[0005] A solid phase synthesis device, comprising: a liquid delivery device, a gas conduit, a piston assembly, a reaction tank, a sampling and venting device, a rotating shaft device, a lower end cover, a waste liquid tank, a temperature control jacket and a delivery pipeline;

[0006] The liquid delivery device includes: a liquid storage tank, a multi-channel selection valve, and a pump; the liquid storage tank is used to store various material solutions, reagents, solvents, etc.; different liquids are selected according to needs to enter the channel through the multi-channel selection valve without cross-contamination risk; the pump pumps the liquid into the reaction tank to control the liquid delivery time and flow rate.

[0007] The gas conduit can be used to introduce compressed air or nitrogen to blow out the residual liquid in the gap between the solid phase carriers in the reaction tank, so as to better clean the solid phase carrier and ensure that the concentration of the material in the next step reaction liquid is not affected. Nitrogen can also be used to pass into the reaction tank to replace the air in the reaction tank to avoid the influence of air on the reaction.

[0008] The piston assembly includes: a piston rod, a piston head, a distributor, a motor, a sieve plate and a sealing ring. The piston assembly is inserted into the interior of the reaction tank and can move up and down along the inner wall of the reaction tank. A first connecting hole is provided on the piston assembly, and the reaction tank is connected to the liquid delivery device and the gas conduit through the first connecting hole. The piston assembly isolates the reaction tank from the outside world through the sealing ring. The distributor can evenly distribute the liquid, so that the solid phase carrier in the cavity can evenly contact the solution during the cleaning process, and the solid phase carrier is cleaned in a flowing manner through the liquid delivery device. The sieve plate aperture is smaller than the solid phase carrier diameter to prevent the solid phase carrier from leaking out.

[0009] The sampling and venting device is placed on the side of the reaction tank, below the piston assembly and above the liquid level during solid phase synthesis;

[0010] The rotating shaft device includes a rotating shaft, a support frame and a motor. The rotating shaft device is connected to the outer wall of the reaction tank. The reaction tank is supported and swung by the rotating shaft device so that the liquid in the reaction tank is evenly distributed in the solid phase carrier.

[0011] The lower end cover includes a sieve plate and a bottom cover. The aperture of the sieve plate is smaller than the diameter of the solid phase carrier to prevent the solid phase carrier from leaking out. A second connecting hole is opened on the lower end cover, and the reaction tank is connected to the waste liquid tank through the second connecting hole.

[0012] Furthermore, the sampling and emptying device is composed of a pipe connected to two valves and is inserted obliquely upward on the side of the reaction tank. When the valve close to the reactor is opened, the other valve away from the reactor is closed. When the reaction tank is tilted toward the sampling and emptying device, the solid phase carrier can flow into the sampling device. When the valve close to the reactor is closed, sampling can be achieved. The two valves on the sampling and emptying device are opened to achieve emptying.

[0013] The beneficial effects of the utility model are:

[0014] (1) The solid phase carrier is compacted during the cleaning process, and the reaction tank and the solid phase carrier are cleaned by flowing liquid, which greatly reduces the use of solvents and can reduce the entire solid phase synthesis solvent by two thirds;

[0015] (2) The piston position is dynamically adjusted according to the expansion of the solid phase carrier during the reaction and cleaning processes, effectively solving the problem that the volume of the reaction tank cannot be adjusted during the traditional continuous flow synthesis process;

[0016] (3) During the reaction process, the volume of the reaction tank is greater than or equal to the volume of the reaction liquid. In the swinging state, the solid phase carrier moves accordingly, which can effectively solve the problem of reaction heterogeneity;

[0017] (4) It can realize closed reaction, isolate oxygen and moisture in the air, and effectively avoid side reactions;

[0018] (5) Sampling and venting ports are set up to solve the sampling problem of traditional reactors and continuous flow synthesis processes;

[0019] (6) Set up an oblique sampling port to prevent the solid phase carrier and reaction liquid from depositing in the sampling port pipeline. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] In order to more clearly illustrate the technical solution of the present invention, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0021] Figure 1 A structural schematic diagram of the utility model;

[0022] Figure 2 This is a schematic diagram of the structure of the piston assembly of the utility model;

[0023] Figure 3 It is a structural schematic diagram of the lower end cover of the utility model.

[0024] Among them, 1-liquid conveying device, 1-1-liquid storage tank, 1-2-multi-channel selection valve, 1-3-pump, 2-gas conduit, 3-piston assembly, 3-1-piston rod, 3-2-piston head, 3-3-distributor, 3-4-sieve plate, 3-5-sealing ring, 3-6-motor, 4 reaction tank, 5-sampling and venting device, 6-rotating shaft device, 6-1 rotating shaft, 6-2 supporting frame, 6-3 motor, 7-lower end cover, 7-1-sieve plate, 7-2-bottom cover, 8-waste liquid tank, 9-temperature control jacket. DETAILED DESCRIPTION

[0025] The following will be combined with the drawings in the embodiments of the utility model to clearly and completely describe the technical solutions in the embodiments of the utility model. Obviously, the described embodiments are only part of the embodiments of the utility model, not all of the embodiments. Based on the embodiments of the utility model, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the utility model.

[0026] like Figure 1As shown, a solid phase synthesis device includes a solid phase synthesis device, including: a liquid delivery device 1, a gas conduit 2, a piston assembly 3, a reaction tank 4, a sampling and emptying device 5, a rotating shaft device 6, a lower end cover 7, a waste liquid tank 8, a temperature control jacket 9 and a delivery pipeline; wherein the liquid delivery device 1 includes: a liquid storage tank 1-1, a multi-channel selection valve 1-2, and a pump 1-3; the piston assembly 3 includes: a piston rod 3-1, a piston head 3-2, a distributor 3-3, a sieve plate 3-4, a sealing ring 3-5 and a motor 3-6, and the piston assembly 3 is inserted into the interior of the reaction tank 4 and can move up and down along the inner wall of the reaction tank 4;

[0027] The piston assembly 3 is provided with a first connecting hole, and the reaction tank 4 is connected with the liquid delivery device 1 and the gas conduit 2 through the first connecting hole; the sampling and emptying device 5 is placed on the side of the reaction tank 4, below the piston assembly and above the liquid level during solid phase synthesis; the sampling and emptying device 5 is composed of a section of pipe connecting two valves, and is inserted obliquely upward on the side of the reaction tank 4;

[0028] The rotating shaft device 6 includes a rotating shaft 6-1, a support frame 6-2 and a motor 6-3. The rotating shaft device 6 is placed and connected to the outer wall of the reaction tank. The reaction tank 4 is supported and swung by the rotating shaft device 6, so that the liquid in the reaction tank is evenly distributed in the solid phase carrier;

[0029] The lower end cover 7 includes a sieve plate 7-1 and a bottom cover 7-2. The aperture of the sieve plate is smaller than the diameter of the solid phase carrier to prevent the solid phase carrier from leaking out. A second connecting hole is opened on the lower end cover 7, and the reaction tank 4 is connected to the waste liquid tank 8 through the second connecting hole.

[0030] The working process of the present invention (for the convenience of description, the solvents, reagents and operating parameters used in the reaction are only for example purposes):

[0031] a) Swelling of solid phase carrier: Open the two valves of the sampling and emptying device 5, turn on the motor 3-6, lift the piston assembly 3 completely through the piston rod 3-1, and pour 153g of solid phase carrier into the cavity of the reaction tank 4. Use the motor 3-6 to cover the reactor with the piston assembly 3 through the piston rod 3-1. Cut the multi-channel switching valve 1-2 to the dissolving and cleaning solvent tank in 1-1, and transport 1500ml of solution to the reaction tank 4 through the pump 1-3, close the sampling and emptying device 5, and turn on the rotating shaft device 6 to swing the reaction tank 4 left and right;

[0032] b) Cleaning of solid phase carrier: Close the sampling and emptying device 5, start the motor 3-6, adjust the piston assembly 3 to contact with the solid phase carrier through the piston rod 3-1, and then press down 0.2 cm again. At this time, the height of the solid phase carrier is about 5.9 cm. Switch the multi-channel switching valve 1-2 to the dissolution and cleaning solvent tank, and transfer 600 ml of solution to the reaction tank 4 through the pump 1-3. The cleaning liquid is discharged from the lower end cover 7 to the waste liquid tank 8. Open the compressed air or nitrogen gas conduit 2 to blow out the residual liquid in the gap between the solid phase carriers in the reaction tank 4;

[0033] c) Solid phase carrier coupling: Open the two valves of the sampling and emptying device 5, start the motor 3-6, lift the piston assembly 3 through the piston rod 3-1, and switch the multi-channel switching valve 1-2 to the material tank, condensing agent tank, and dissolving solution tank in 1-1 in turn, and transfer a total of 800 ml of each solution to the reaction tank 4 through the pump 1-3. Make a gap of 1-3 cm between the piston assembly 3 and the liquid surface, and the total height of the reaction tank 4 cavity is between 8-10 cm. Close the sampling and emptying device 5. Turn on the rotating shaft device 6 to swing the reaction tank 4 left and right;

[0034] d) Solid phase carrier detection: open the valve of the sampling and emptying device 5 close to the reaction tank, and close the other valve away from the reaction tank. When the reaction tank 4 swings to a horizontal state, close the two valves on the sampling and emptying device 5. Swing the reaction tank 4 to an upright state again, keep the valve close to the reaction tank 4 closed, open the valve away from the reaction tank 4, perform sampling and detection, and proceed to the next step after the reaction is completed;

[0035] e) Cleaning of the solid phase carrier after coupling: Close the sampling and venting device 5, start the motor 3-6, adjust the piston assembly 3 to contact with the solid phase carrier through the piston rod 3-1, and then press down 0.2 cm again. At this time, the height of the solid phase carrier is about 6.0 cm. Switch the multi-channel switching valve 1-2 to the dissolution and cleaning solvent tank, and transfer 600 ml of solution to the reaction tank 4 through the pump 1-3. The cleaning liquid is discharged from the lower end cover 7 to the waste liquid tank 8. Open the compressed air or nitrogen gas conduit 2 to blow out the residual liquid in the gap between the solid phase carriers in the reaction tank 4;

[0036] f) Deprotection: Open the two valves of the sampling and venting device 5, start the motor 3-6, lift the piston assembly 3 through the piston rod 3-1, switch the multi-channel switching valve 1-2 to the deprotection liquid tank, and transfer 1500ml of solution to the reaction tank 4 through the pump 1-3. Make a 1-3cm gap between the piston assembly 3 and the liquid surface, and close the sampling and venting device 5. Turn on the rotating shaft device 6 to make the reaction tank 4 swing left and right;

[0037] g) Solid phase carrier detection: open the valve of the sampling and emptying device 5 close to the reaction tank, and close the other valve away from the reaction tank. When the reaction tank 4 swings to a horizontal state, close the two valves on the sampling and emptying device 5. Swing the reaction tank 4 to an upright state again, keep the valve close to the reaction tank 4 closed, open the valve away from the reaction tank 4, perform sampling and detection, and proceed to the next step after the reaction is completed;

[0038] h) Cleaning after deprotection: Close the sampling and venting device 5, start the motor 3-6, adjust the piston assembly 3 to contact with the solid phase carrier through the piston rod 3-1, and then press it down again by 0.2 cm to ensure that the solid phase carrier is about 5.9 cm high at this time. Switch the multi-channel switching valve 1-2 to the cleaning solvent tank, and transfer 900 ml of solution to the reaction tank 4 through the pump 1-3. The cleaning liquid is discharged from the lower end cover 7 to the waste liquid tank 8. Open the compressed air or nitrogen gas conduit 2 to blow out the residual liquid in the gap between the solid phase carriers in the reaction tank 4;

[0039] i) Repeat steps c, d, e, f, g, and h in a cyclic operation to couple the solid phase carrier until all sequences are connected. During the process, the height of the piston assembly 3 needs to be adjusted according to the actual situation.

[0040] j) When the reaction needs to be carried out in a closed manner, the sampling and venting device 5 can be closed, and the piston assembly 3 and the liquid delivery device 1 can be operated at the same time; when nitrogen filling protection is required, the sampling and venting device 5 is opened, and nitrogen is used to replace the air inside the reaction tank 4;

[0041] k) Repeat the coupling operation once, i.e., steps c, d, e, f, g, and h, using 3800 ml of solvent.

[0042] Comparative Example

[0043] a) Swelling of solid phase carrier: Use a glass reaction tank, pour 150g of solid phase carrier into it, add 1500ml of solvent, and stir to swell the solid phase carrier;

[0044] b) Cleaning of the solid phase carrier: Use a vacuum drain device at the bottom to suck the reaction liquid. After draining, add 900 ml of solution, stir and drain again, repeat this operation four times, and use a total of 3600 ml of solution;

[0045] c) Solid phase support coupling: Add the dissolved material solution and condensation agent, a total of 800 ml, into the reaction tank. Start stirring and perform coupling;

[0046] d) Solid phase carrier detection: Sampling and detection are performed, and when the reaction is shown to be complete, the next step is entered;

[0047] e) Cleaning the solid phase carrier after coupling: Use a vacuum drain device at the bottom to suck the reaction liquid. After draining, add 1200 ml of solution, stir and drain again, repeat this operation four times, and use a total of 4800 ml of solution;

[0048] f) Deprotection: Add 1500 ml of deprotection solution into the reaction tank. Start stirring to deprotect the solid phase carrier;

[0049] g) Solid phase carrier detection: Sampling and detection are performed. If the deprotection is completed, proceed to the next step;

[0050] h) Post-deprotection cleaning: Use a vacuum drain device at the bottom to suck the reaction solution. After draining, add 1200 ml of solution, stir and drain again, repeat this operation seven times, using a total of 8400 ml of solution;

[0051] i) Repeat steps c, d, e, f, g, and h to carry out coupling until the sequential coupling is completed. The coupling operation is repeated once, i.e., steps c, d, e, f, g, and h, and the amount of solvent used is 15500 ml.

[0052] By comparison, it can be seen that the practical solid phase synthesis device uses 3800 ml of solvent, compared with the traditional glass reaction tank that uses 15500 ml of solvent, and each reaction can save 75% of the solvent usage.

[0053] The "upper" and "lower" directions in the present invention refer to the upper and lower directions in nature when in use.

[0054] The above disclosure is only a preferred embodiment of the present invention, and certainly cannot be used to limit the scope of rights of the present invention. Therefore, equivalent changes made according to the claims of the present invention are still within the scope covered by the present invention.

Claims

1. A solid phase synthesis device, comprising: A liquid conveying device (1), a gas conduit (2), a piston assembly (3), a reaction tank (4), a sampling and emptying device (5), a rotating shaft device (6), a lower end cover (7), a waste liquid tank (8), a temperature control jacket (9) and a conveying pipeline; characterized in that: the liquid conveying device (1) comprises: a liquid storage tank (1-1), a multi-channel selection valve (1-2), and a pump (1-3); The piston assembly (3) comprises: a piston rod (3-1), a piston head (3-2), a distributor (3-3), a sieve plate (3-4), a sealing ring (3-5) and a motor (3-6); the piston assembly (3) is inserted into the interior of the reaction tank (4) and can move up and down along the inner wall of the reaction tank (4); a first connecting hole is provided on the piston assembly (3), and the reaction tank (4) is connected with the liquid conveying device (1) and the gas conduit (2) through the first connecting hole; The sampling and emptying device (5) is placed on the side of the reaction tank (4), below the piston assembly and above the liquid level during solid phase synthesis; The rotating shaft device (6) comprises a rotating shaft (6-1), a support frame (6-2) and a motor (6-3); the rotating shaft device (6) is connected to the outer wall of the reaction tank; the reaction tank (4) is supported and swung by the rotating shaft device (6) so that the liquid in the reaction tank is evenly distributed in the solid phase carrier; The lower end cover (7) comprises a sieve plate (7-1) and a bottom cover (7-2); the sieve plate has a smaller aperture than the solid phase carrier to prevent the solid phase carrier from leaking out; a second connecting hole is provided on the lower end cover (7); the reaction tank (4) is connected to the waste liquid tank (8) via the second connecting hole.

2. The solid phase synthesis device according to claim 1, characterized in that The sampling and venting device (5) is composed of a section of pipe connected to two valves and is inserted obliquely upwards on the side of the reaction tank (4).

Images