CN114732918A

CN114732918A - Production equipment of liquid composition and preparation method and application thereof

Info

Publication number: CN114732918A
Application number: CN202210651266.7A
Authority: CN
Inventors: 王跃; 张颖; 张爱丽; 徐新盛
Original assignee: Beijing Cotimes Biotech Co Ltd
Current assignee: Beijing Cotimes Biotech Co Ltd
Priority date: 2022-06-10
Filing date: 2022-06-10
Publication date: 2022-07-12
Anticipated expiration: 2042-06-10
Also published as: WO2023237092A1; CN114732918B

Abstract

The present application provides a process for producing trans-2- [2- (5-)¹⁸F]Fluorotridecyl) cyclopropyl]An apparatus for the production of acetic acid (hereinafter referred to as "compound i") liquid compositions, a method for the production thereof and use thereof, specifically to provide an apparatus for the production comprising: a pre-processing module for enriching¹⁸F ions; the reaction module is used for reacting to obtain a crude product of the compound I; the purification module is used for purifying the crude product of the compound I to obtain a pure product of the compound I; and a prescription module for enriching and prescribing the purified compound I pure product into a compound I liquid composition. And provides a corresponding using method and application. The technical scheme of the application can prepare a crude compound I product, and further purify, enrich and formulate the crude compound I product to prepare a liquid compound I composition for direct clinical application. And, canThe automation of the apparatus is realized by controlling the valves and the like by a microprocessor and the like.

Description

Production equipment of liquid composition and preparation method and application thereof

Technical Field

The application relates to the technical field of radiopharmaceuticals, in particular to production equipment of a liquid composition, a preparation method and application thereof.

Background

According to data reported by research of Chinese disease prevention and control center, the proportion and absolute number of coronary heart disease deaths in the Chinese population to the total deaths are remarkably improved, the total number of coronary heart disease deaths in the Chinese population in 2013 is 139.4 thousands, and the number of coronary heart disease deaths is increased by 90% compared with that in 1990. At present, coronary heart disease becomes the first cause of death in six provinces and direct prefecture city/provincial administrative regions in China. With the progress of aging, the number of the coronary heart disease and the number of deaths in China will be increased continuously.

With the development of clinical cardiology, the focus of attention has also shifted from the original coronary artery disease diagnosis to the risk stratification and prognosis judgment. At present, it is generally believed that information such as myocardial ischemia, cardiac function and viable myocardium can provide a main basis for coronary artery disease risk stratification, prognosis judgment and treatment scheme formulation. Therefore, identification of viable myocardium is of great clinical significance, and is a hotspot for clinical treatment and prediction of related events. At present, nuclide myocardial imaging remains the gold standard for in vivo assessment of viable myocardium.

Trans-2- [2- (5-, [ solution ]¹⁸F]Fluorotridecyl) cyclopropyl]Acetic acid (trans-2- [2- (5- ], salt thereof, and hydrate thereof¹⁸F]fluorotricycl) cyclopropy) acetic acid; hereinafter referred to as "compound I") is a radionuclide¹⁸The Modified Fatty Acid (MFA) marked by F has a structure similar to that of Free Fatty Acid (FFA) naturally existing in human bodies, can be taken up by myocardial cells and is used for Positron Emission Tomography (PET) to evaluate the activity of the myocardial cells. The structure of the compound I is shown as the following figure:

the compound I can be imaged 5 minutes after intravenous injection, and has high compliance and clinical benefit.

At present, the non-fully automatic production mode cannot carry out complete radiation protection, and the manual labeling cannot prepare large-batch (radioactivity) liquid compound I compositions (such as injection), and the single preparation can only meet the use requirement of 1-2 people, so the clinical use is limited.

Therefore, it is important to develop an automated apparatus for producing a liquid composition of compound I (e.g., an injection solution).

Disclosure of Invention

To solve the problems of the prior art, the present application provides a process for producing trans-2- [2- (5-, [2 ], [2- ]¹⁸F]Fluorotridecyl) cyclopropyl]Apparatus for acetic acid liquid compositions (e.g., injection solutions), methods of making, and uses thereof. The technical scheme of the application is as follows:

1. an apparatus for producing a liquid composition of compound i comprising:

a pre-processing module for enriching¹⁸F ions;

reaction module for enriched¹⁸Reacting F ions with a precursor of the compound I to generate a compound I tert-butyl ester, and performing a tert-butyl esterification reaction on the compound I tert-butyl ester to obtain a crude product of the compound I;

the purification module is used for purifying the crude product of the compound I to obtain a pure product of the compound I;

a prescription module, which enriches and prescriptively prepares a purified product of the compound I into a liquid composition of the compound I;

compound I

2. The apparatus of item 1, the pre-processing module comprising:

the first valve to the sixth valve respectively comprise at least a first interface, a second interface and a third interface, and any two interfaces of the three interfaces can be conducted or none of the three interfaces can be conducted by the first valve to the sixth valve; the first interface of the first valve is connected with the first positive pressure pipeline, the second interface of the first valve is connected with the first interface of the second valve, the second interface of the second valve is connected with the first interface of the third valve, the second interface of the third valve is connected with the first interface of the fourth valve, the second interface of the fourth valve is connected with the first interface of the fifth valve, and the second interface of the fifth valve is connected with the first interface of the sixth valve;

the first recovery container is respectively connected with the first negative pressure pipeline and the third interface of the first valve;

a first reagent container connected to the third port of the second valve;

a first injector connected to the third port of the third valve;

¹⁸an F ion enrichment bin connected between the third port of the fourth valve and the third port of the fifth valve;

the second injector is connected with the third interface of the sixth valve;

preferably, the first valve, the second valve, the third valve, the fourth valve, the fifth valve and the sixth valve are all electrically controlled valves.

3. The apparatus of item 2, the pre-processing module further comprising:

the first linear driving device can drive the piston of the first syringe to move in the hollow cylinder;

the second linear driving device can drive the piston of the second injector to move in the hollow cylinder;

preferably, the first linear driving device and the second linear driving device are selected from one of a pneumatic rod, a hydraulic rod and a lead screw;

further preferably, the first linear driving device and the second linear driving device are both lead screws, and the lead screws are driven by stepping motors.

4. The apparatus according to item 2, wherein the positive pressure negative pressure pipeline and the charging pipeline respectively extend into the second syringe through the piston of the second syringe;

preferably, a flow meter is arranged on the liquid feeding pipeline.

5. The apparatus of item 2, the reaction module comprising:

the system comprises a seventh valve, an eighth valve, a ninth valve, a tenth valve, an eleventh valve and a tenth valve, wherein the seventh valve to the twelfth valve respectively at least comprise a first interface, a second interface and a third interface, and the seventh valve to the twelfth valve can realize the conduction of any two interfaces in the three interfaces or make the three interfaces non-conductive; the first interface of the seventh valve is connected with the pretreatment module, the second interface of the seventh valve is connected with the first interface of the eighth valve, the second interface of the eighth valve is connected with the first interface of the ninth valve, the second interface of the ninth valve is connected with the first interface of the tenth valve, the second interface of the tenth valve is connected with the first interface of the eleventh valve, the second interface of the eleventh valve is connected with the first interface of the tenth valve, and the third interface of the tenth valve is connected with the purification module;

the reaction container is respectively connected with a second negative pressure pipeline and a third interface of the seventh valve;

the temperature control assembly is used for heating and/or cooling the reaction container;

a third syringe connected to the third port of the eighth valve;

a second reagent container connected to the third port of the ninth valve;

a third reagent container connected to the third port of the tenth valve;

a fourth syringe connected to the third port of the eleventh valve;

preferably, the seventh valve, the eighth valve, the ninth valve, the tenth valve, the eleventh valve and the twelfth valve are all electrically controlled valves.

6. The apparatus of clause 5, the reaction module further comprising:

the third linear driving device can drive the piston of the third syringe to move in the hollow cylinder;

the fourth linear driving device can drive a piston of the fourth syringe to move in the hollow cylinder;

preferably, the third linear driving device and the fourth linear driving device are selected from one of a pneumatic rod, a hydraulic rod and a lead screw;

further preferably, the third linear driving device and the fourth linear driving device are both screw rods, and the screw rods are driven by stepping motors.

7. The apparatus of clause 5, the purification module comprising:

the seventeenth valve at least comprises a first interface, a second interface, a third interface, a fourth interface, a fifth interface and a sixth interface, wherein the seventeenth valve can be switched between a first mode and a second mode, the first mode is that the first interface is communicated with the second interface, the third interface is communicated with the fourth interface, and the fifth interface is communicated with the sixth interface; the second mode is that the second interface is communicated with the third interface, the fourth interface is communicated with the fifth interface, and the sixth interface is communicated with the first interface; a fourth interface of the seventeenth valve is connected with the reaction module;

one end of the chromatographic column assembly is connected with the second interface of the seventeenth valve;

the two ends of the quantitative ring are respectively connected with the third interface of the seventeenth valve and the sixth interface of the seventeenth valve;

the liquid conveying pump is connected with the first interface of the seventeenth valve;

the second recovery container is connected with a fifth interface of the seventeenth valve;

the eighteenth valve at least comprises a first interface, a second interface and a third interface, and the eighteenth valve can realize the conduction of the first interface and the second interface or the conduction of the first interface and the third interface; the first interface of the eighteenth valve is connected with the other end of the chromatographic column assembly, the second interface of the eighteenth valve is connected with the prescription module, and the third interface of the eighteenth valve is connected with the second recovery container;

preferably, the seventeenth valve and the eighteenth valve are both electrically controlled valves.

8. The apparatus of item 7, the prescribing module comprising:

a thirteenth valve, a fourteenth valve, a fifteenth valve, a sixteenth valve, a nineteenth valve, a twentieth valve, a twenty-first valve, a twentieth valve, and a twentieth valve, wherein the thirteenth to sixteenth valves and the nineteenth to twentieth valves respectively include at least a first interface, a second interface, and a third interface, and the thirteenth to sixteenth valves and the nineteenth to twentieth valves are capable of conducting any two of the three interfaces or not conducting any three interfaces; wherein the first interface of the thirteenth valve is connected with the second interface of the twelfth valve, the second interface of the thirteenth valve is connected with the first interface of the fourteenth valve, the second interface of the fourteenth valve is connected with the first interface of the fifteenth valve, the second interface of the fifteenth valve is connected with the first interface of the sixteenth valve, the second interface of the sixteenth valve is connected with the first interface of the nineteenth valve, the second interface of the nineteenth valve is connected with the first interface of the twentieth valve, the second interface of the twentieth valve is connected with the first interface of the twenty-first valve, the second interface of the twenty-first valve is connected with the first interface of the twentieth valve, the second interface of the twentieth valve is connected with the first interface of the twentieth valve, and the second interface of the twentieth valve is connected with a fourth negative pressure pipeline, a third port of the twentieth valve is connected to the purification module;

a fifth injector connected to the third port of the thirteenth valve;

a fourth reagent container connected to the third port of the fourteenth valve;

a fifth reagent container connected to the third port of the fifteenth valve;

a sixth reagent container connected to the third port of the sixteenth valve;

the first transfer container is connected with the third interface of the nineteenth valve;

the second transfer container is respectively connected with a third interface of the twentieth valve and a third negative pressure pipeline;

a compound i enrichment bin connected between the third port of the twentieth valve and the third port of the twenty-first valve;

and the finished product collecting container is connected with the second transfer container.

9. The apparatus of item 8, the prescribing module further comprising:

the fifth linear driving device can drive the piston of the fifth syringe to move in the hollow cylinder;

preferably, the fifth linear driving device is selected from one of a pneumatic rod, a hydraulic rod and a lead screw;

further preferably, the fifth linear driving device is a lead screw, and the lead screw is driven by a stepping motor.

10. A method for producing a liquid composition of compound i using the apparatus as described in any one of items 1 to 9 above, comprising:

enrichment using a pre-processing module¹⁸F ions;

enriching using reaction modules¹⁸Reacting F ions with a precursor of the compound I to generate a compound I tert-butyl ester, and performing a tert-butyl esterification reaction on the compound I tert-butyl ester to obtain a crude product of the compound I;

purifying the crude product of the compound I by using a purification module to obtain a pure product of the compound I;

the purified pure compound i was enriched using a formulation module and formulated into a compound i liquid composition.

11. Use of the apparatus of any one of items 1 to 9 in the production of a compound i liquid composition.

The present application provides a process for producing trans-2- [2- (5-, [2 ])¹⁸F]Fluorotridecyl) cyclopropyl]The equipment for preparing the liquid composition of the acetic acid (compound I) can prepare crude compound I, and the crude compound I is purified, enriched and formulated to prepare the liquid composition of the compound I for direct clinical application. Moreover, the automation of the equipment can be realized by controlling each valve and the like through a microprocessor system (such as PLC and the like). Meanwhile, the application provides a method for using the equipment and application.

The above description is only an overview of the technical solutions of the present application, and in order to make the technical means of the present application more clearly understood, the present application is described below in the following detailed description of the present application in order to make the implementation of the technical means of the present application possible to a person skilled in the art according to the content of the present specification, and in order to make the above and other objects, features, and advantages of the present application more obvious.

Drawings

FIG. 1: the pre-processing module, the reaction module and the prescription module of the production equipment are assembled schematically.

FIG. 2(a) to FIG. 2 (b): purification module schematic of the production facility (purification module performs purification by switching between fig. 2(a) mode and fig. 2(b) mode).

FIG. 3(a) to FIG. 3 (h): the schematic structure of the three-way valve (fig. 3(a) is a schematic diagram of three ports in the three-way valve being communicated, fig. 3(b) to 3(d) are schematic diagrams of two ports in the three-way valve being communicated, respectively, and fig. 3(e) to 3(h) are schematic diagrams of three ports in the three-way valve being not communicated with each other, respectively).

FIG. 4(a) to FIG. 4 (d): is a schematic diagram of the three-way valve of fig. 3 (fig. 4(a) is a schematic diagram of the three-way valve corresponding to fig. 3 (b); fig. 4(b) is a schematic diagram of the three-way valve corresponding to fig. 3 (c); fig. 4(c) is a schematic diagram of the three-way valve corresponding to fig. 3 (d); and fig. 4(d) is a schematic diagram of the three-way valve corresponding to fig. 3(e) to 3 (h)).

FIG. 5(a) to FIG. 5 (b): the six-way valve is schematically shown in the structure (fig. 5(a) and 5(b) are respectively schematic diagrams of the valve core of the six-way valve in different working positions).

Fig. 6(a) to 6 (c): schematic diagram of the working principle of the pre-processing module (the pre-processing module is implemented according to the sequence of FIG. 6(a) to FIG. 6 (c))¹⁸F ions are enriched and sent to the reaction module).

FIG. 7(a) to FIG. 7 (g): the reaction module is schematically represented in the working principle (the reaction modules carry out the reactions according to the sequence of FIGS. 7(a), 7(b), 7(c), 7(b), 7(d), 7(c), 7(b), 7(e), 7(f) and 7 (g)).

FIG. 8(a) to FIG. 8 (h): the working principle of the prescription module is shown schematically (the prescription module is enriched and prescribed according to the sequence of fig. 8(a), 8(b), 8(c), 8(d), 8(b), 8(d), 8(e), 8(f), 8(g), 8(f) and 8 (h)).

FIG. 9: the total negative pressure pipeline is connected with a schematic diagram.

Description of reference numerals:

1-23, first-twentieth valves; v1, three-way valve body; v2, three-way valve spool; v3, six-way valve body; v4, six-way valve core;

24. a first recovery tank; 25. a first reagent container; 26. a first syringe; 27.¹⁸f, an ion enrichment bin; 28. a second syringe; 29. a positive pressure and negative pressure pipeline; 30. a liquid feeding pipeline;

31. a reaction vessel; 32. a third syringe; 33. a second reagent container; 34. a third reagent container; 35. a fourth syringe;

36. a chromatography column assembly; 37. a dosing ring; 38. a liquid delivery pump; 39. a second recovery vessel;

40. a fifth syringe; 41. a fourth reagent container; 42. a fifth reagent container; 43. a sixth reagent container; 44. a first transfer vessel; 45. a second transfer vessel; 46. a compound I enrichment bin; 47. a finished product collection container;

48. a third recovery vessel;

p0, a positive pressure pipeline of the positive pressure and negative pressure pipeline; p1, a first positive pressure line;

n, a total negative pressure pipeline; n0, a negative pressure pipeline of the positive pressure negative pressure pipeline; n1, a first negative pressure pipeline; n2, a second negative pressure pipeline; n3, a third negative pressure pipeline; n4, a fourth negative pressure pipeline.

Detailed Description

The following embodiments of the present application are merely illustrative of specific embodiments for carrying out the present application and should not be construed as limiting the present application. Other changes, modifications, substitutions, combinations, and simplifications which may be made without departing from the spirit and principles of the present application are intended to be equivalent substitutions and are within the scope of the present application.

This example provides a process for producing trans-2- [2- (5-, [2 ]¹⁸F]Fluorotridecyl) cyclopropyl]An apparatus for the preparation of a liquid composition (e.g., an injection) of acetic acid (hereinafter "compound i"), comprising:

a pre-processing module for enriching¹⁸F ions;

reaction module forAfter enrichment¹⁸Reacting F ions with a precursor of the compound I to generate a compound I tert-butyl ester, and performing a tert-butyl esterification reaction on the compound I tert-butyl ester to obtain a crude product of the compound I;

and a prescription module for enriching and prescribing the purified compound I pure product into a compound I liquid composition.

As shown in the following figure, Compound I is prepared by reacting a precursor of Compound I with radioactive fluorine [, [ solution ] or a salt thereof¹⁸F]The ion is used as the starting material and is prepared by two steps of reaction. The first step is fluorine [ alpha ], [ alpha ] and [ alpha ], [ alpha ] an¹⁸F]Nucleophilic substitution of mesyloxy group in the precursor of compound I to obtain tert-butyl ester of compound I. And secondly, adding a dichloromethane solution containing trifluoroacetic acid without separation and purification to carry out a tert-butylation reaction to obtain a crude product of the compound I. The synthetic route of the crude compound I is shown in the following figure.

In the figure, K₂₂₂Is 4,7,13,16,21, 24-hexaoxy-1, 10-diazabicyclo [8.8.8]Hexacosane, abbreviated as aminopolyether.

This example shows an apparatus for producing a liquid composition of compound I (e.g., an injection solution) which is first enriched by a pre-treatment module¹⁸F ions; after enrichment¹⁸F ions enter a reaction module, then react with a compound I precursor in the reaction module to generate a compound I tert-butyl ester, and further perform a tert-butylation reaction on the compound I tert-butyl ester to obtain a compound I crude product; purifying the crude product of the compound I in a purification module to obtain a pure product of the compound I; further, the pure compound I enters a prescription module for enrichment and further prescription into a compound I liquid composition.

Through the technical scheme of the embodiment, the crude compound I can be obtained, and the crude compound I is purified, enriched and formulated to be directly used in clinic.

In addition, the term "crude product" and "pure product" in the present application refer to the product before and after purification, respectively; the prescription in the embodiment specifically refers to that a pure compound I and auxiliary materials are prepared into a compound I liquid composition.

In one embodiment, the preprocessing module as described in fig. 1, 3, 4 and 6 includes:

the valve comprises a first valve 1, a second valve 2, a third valve 3, a fourth valve 4, a fifth valve 5 and a sixth valve 6, wherein the first valve 1 to the sixth valve 6 respectively at least comprise a first interface, a second interface and a third interface, and the first valve 1 to the sixth valve 6 can realize the conduction of any two interfaces in the three interfaces or make the three interfaces non-conductive; the first port of the first valve 1 is connected to a first positive pressure line P1, the second port of the first valve 1 is connected to the first port of the second valve 2, the second port of the second valve 2 is connected to the first port of the third valve 3, the second port of the third valve 3 is connected to the first port of the fourth valve 4, the second port of the fourth valve 4 is connected to the first port of the fifth valve 5, and the second port of the fifth valve 5 is connected to the first port of the sixth valve 6;

the first recovery container 24 is respectively connected with the first negative pressure pipeline N1 and the third port of the first valve 1;

a first reagent container 25 connected to the third port of the second valve 2, the first reagent container 25 being used for containing¹⁸F leacheate (e.g. acetonitrile + water + K)₂₂₂+K₂CO₃Etc.);

a first injector 26 connected to the third port of the third valve 3;

¹⁸an F ion enrichment bin 27 connected between the third port of the fourth valve 4 and the third port of the fifth valve 5, the¹⁸The F ion enrichment bin 27 is filled with anion exchange resin;

a second syringe 28 connected to the third port of the sixth valve 6;

preferably, the first valve 1, the second valve 2, the third valve 3, the fourth valve 4, the fifth valve 5 and the sixth valve 6 are all electrically controlled valves.

First, as shown in fig. 3, a three-way valve is provided, which can realize the functions of the first to sixth valves 1 to 6, and certainly can also realize the functions of the seventh to sixteenth valves 7 to 16 and the nineteenth to twentieth valves 23, which will not be described in detail below.

Specifically, as shown in fig. 3(a) to 3(h), the three-way valve includes a three-way valve spool V2 having a circular cross section, and a three-way valve body V1 outside the three-way valve spool V2, the three-way valve body V1 is provided with a first port on the left side, a second port on the right side, a third port on the upper side, and a T-shaped flow channel is provided in the three-way valve spool V2. By rotating the valve plug V2, the first port (i) can be communicated with the third port (shown in fig. 3 (b)), the first port (i) can be communicated with the second port (i) (shown in fig. 3 (c)), the second port (i) can be communicated with the third port (i) (shown in fig. 3 (d)), and the three ports are not communicated (shown in fig. 3(e) -3 (h)). In addition, given the above three-way valve structure, those skilled in the art know from the prior art how to control the three-way valve spool V2 to rotate a fixed angle relative to the three-way valve V1 to achieve electrical (electromagnetic) control of the three-way valve (e.g., setting a stepper motor to control the rotation of the three-way valve spool V2). In addition, in order to be able to briefly describe the state of the three-way valve in the following, fig. 4 gives a schematic view of the three-way valve in fig. 3, wherein fig. 4(a) is a schematic view of the three-way valve corresponding to fig. 3 (b); FIG. 4(b) is a schematic view of a three-way valve corresponding to FIG. 3 (c); FIG. 4(c) is a schematic view of a three-way valve corresponding to FIG. 3 (d); fig. 4(d) is a schematic diagram of the three-way valve corresponding to fig. 3(e) to 3 (h).

In addition, the first negative pressure pipeline N1 specifically provides negative pressure through vacuum pumping, and the negative pressure pipeline N0, the second negative pressure pipeline N2, the third negative pressure pipeline N3 and the fourth negative pressure pipeline N4 of the positive pressure negative pressure pipeline below can also provide negative pressure through vacuum pumping, which is not described again below. And the negative pressure pipeline N0, the first negative pressure pipeline N1, the second negative pressure pipeline N2, the third negative pressure pipeline N3 and the fourth negative pressure pipeline N4 of the positive pressure negative pressure pipeline may be connected to one vacuum-pumping device alone, or two or more of them may be connected to one vacuum-pumping device/pipeline. Specifically, as shown in fig. 9, the third recovery tank 48 is connected to the total negative pressure line N, and other negative pressure lines (more than one of the negative pressure line N0 of the positive pressure negative pressure line, the first negative pressure line N1, the second negative pressure line N2, the third negative pressure line N3, and the fourth negative pressure line N4) are also connected to the third recovery tank 48 (specifically, connected to the left side of the third recovery tank 48 in fig. 9), so that one vacuum-pumping device can drive more than one negative pressure line to operate, and the third recovery tank 48 can store the liquid flowing from the negative pressure line.

The first positive pressure line P1 provides positive pressure by blowing out inert gas (such as nitrogen, argon, etc.), and a filter membrane may be installed in the first positive pressure line P1 to ensure the cleanness of the inert gas entering the equipment. The positive pressure line P0 of the following positive pressure and negative pressure line may also provide positive pressure in this manner, and will not be described in detail below.

Moreover, as known by those skilled in the art, generally, control valves (e.g., electric control valves, specifically electromagnetic valves) may be disposed on the negative pressure pipeline N0, the first negative pressure pipeline N1, the second negative pressure pipeline N2, the third negative pressure pipeline N3, the fourth negative pressure pipeline N4, the positive pressure pipeline P0 of the positive pressure negative pressure pipeline, and the first positive pressure pipeline P1 to control the on/off of the pipelines, and/or a flow valve/flow meter to control the magnitude of the positive pressure/negative pressure, and so on, which are not described herein again.

The person skilled in the art knows that the hollow cylinder, the piston inside the hollow cylinder, is an essential component structure of the syringe. The piston can be in a long strip-shaped structure, and the piston and the hollow cylinder can move relatively by pushing the part of the piston, which is positioned outside the hollow cylinder; the piston can also be only a rubber head which has a sealing effect and is positioned in the hollow cylinder, and at the moment, the piston can be provided with a core rod, and the piston and the hollow cylinder can be driven to move relatively by pushing the core rod. As shown in FIG. 1, the structure of the syringe is shown to consist of an empty barrel, a plunger and a core rod.

Pre-processing module enrichment¹⁸The specific process of F ion can be as shown in fig. 6(a) -6 (c),

first, the first to sixth valves 1 to 6 are in the states shown in FIG. 6(a) As shown, the first negative pressure line N1 is evacuated. The second syringe 28 will contain¹⁸Oxygen [ alpha ] of F ion¹⁸O]Eighteen water is discharged, containing¹⁸Oxygen [ alpha ] of F ion¹⁸O]Eighteen water flows through¹⁸When the F ion-enriching bin 27 is in use,¹⁸f ion is in¹⁸The F ion enrichment bin 27 is used for enrichment, and the rest liquid flows into the first recovery container 24;

thereafter, as shown in FIG. 6(b), the second to third valves 2 to 3 are in the state in which the first syringe 26 is drawn into the first reagent container 25¹⁸F, leacheate;

finally, the third to sixth valves 3 to 6 are in the state shown in FIG. 6(c), and the first syringe 26 is filled with the liquid¹⁸F when the leacheate is pushed out, then¹⁸F leacheate will be enriched in¹⁸In the F ion enrichment bin¹⁸F ions are sent to the reaction module.

This embodiment provides a specific preprocessing module, which can be easily and conveniently implemented¹⁸F ions are enriched and the enriched F ions are¹⁸The F ions are sent to the subsequent reaction module. Especially when the valves, the positive pressure pipeline, the negative pressure pipeline and the injector are automatically controlled, the automatic control of the valves, the positive pressure pipeline, the negative pressure pipeline and the injector can be realized¹⁸F ion enrichment and automatic treatment of the F ion is sent to a reaction module.

In one embodiment, the pre-processing module further comprises:

a first linear drive (not shown in the drawings) capable of moving the piston of the first syringe 26 inside the hollow cylinder;

a second linear drive (not shown in the drawings) capable of moving the piston of the second syringe 28 inside the hollow cylinder;

In the present embodiment, the first and second linear driving devices are provided to control the first and

second syringes

26 and 28.

When the pneumatic rod and the hydraulic rod are used for matching with controllers such as a PLC and the like, the automatic control of the first injector 26 and the second injector 28 is conveniently realized.

By using the lead screw, the strokes of the pistons in the first syringe 26 and the second syringe 28 can be accurately controlled, and especially when the lead screw is driven by a stepping motor, the lead screw is conveniently matched with a controller such as a PLC to realize automatic and accurate control of the first syringe 26 and the second syringe 28. The lead screw driven by the stepping motor can be assembled by the user, and an electric push rod (a lead screw system) finished product can be directly purchased.

In one embodiment, as shown in fig. 1, the positive pressure and negative pressure line 29 and the charging line 30 respectively extend through the piston of the second syringe 28 into the closed space formed by the piston of the second syringe 28 and the empty cylinder;

preferably, the liquid feeding pipeline 30 is provided with a flow meter so as to control the liquid feeding amount, and/or the liquid feeding pipeline 30 is provided with a control valve (such as an electric control valve, specifically, an electromagnetic valve) which can control the on-off of the pipeline so as to control whether to feed liquid or not.

In the present application, the positive pressure and negative pressure pipeline 29 is a positive pressure pipeline P0 of the positive pressure and negative pressure pipeline, and the negative pressure pipeline N0 of the positive pressure and negative pressure pipeline are connected to one pipeline, and the one pipeline penetrates through the piston (as shown in fig. 1); or the positive pressure pipeline P0 of the positive pressure and negative pressure pipeline and the negative pressure pipeline N0 of the positive pressure and negative pressure pipeline respectively penetrate through the piston.

The present application thus provides a means for filling the second syringe 28 (including¹⁸Oxygen [2 ] of F ion¹⁸O]Eighteen water), and in order to prevent the pressure in the second syringe 28 from being too high, the negative pressure pipeline N0 of the positive pressure and negative pressure pipeline is vacuumized, so as to implement liquid feeding. After filling, the liquid in the second syringe 28 can be discharged for subsequent reaction by pushing the piston down/through the positive pressure line P0 of the positive pressure/negative pressure line.

This example shows a solution for filling the second syringe 28. FromWhile more can be provided¹⁸Oxygen [2 ] of F ion¹⁸O]Eighteen water to¹⁸F ion enrichment provides more and continuous subsequent reactions¹⁸And F ions. And the positive pressure pipeline P0 of the positive pressure and negative pressure pipeline can provide positive pressure to charge the subsequent process or push the piston to charge the subsequent process more accurately.

In one embodiment, as shown in fig. 1, the reaction module comprises:

the valve assembly comprises a seventh valve 7, an eighth valve 8, a ninth valve 9, a tenth valve 10, an eleventh valve 11 and a twelfth valve 12, wherein the seventh valve 7 to the twelfth valve 12 respectively comprise at least a first interface, a second interface and a third interface, and the seventh valve 7 to the tenth valve 12 can realize the conduction of any two interfaces in the three interfaces or make the three interfaces non-conductive; the first port of the seventh valve 7 is connected to the pre-treatment module (the second port of the sixth valve 6), the second port of the seventh valve 7 is connected to the first port of the eighth valve 8, the second port of the eighth valve 8 is connected to the first port of the ninth valve 9, the second port of the ninth valve 9 is connected to the first port of the tenth valve 10, the second port of the tenth valve 10 is connected to the first port of the eleventh valve 11, the second port of the eleventh valve 11 is connected to the first port of the twelfth valve 12, and the third port of the twelfth valve 12 is connected to the fourth port of the seventeenth valve 17);

the reaction vessel 31 is connected to the second negative pressure pipeline N2 and the third port of the seventh valve 7, respectively, wherein a control valve (such as an electric control valve, specifically, an electromagnetic valve) is preferably disposed on a pipeline between the second negative pressure pipeline N2, the reaction vessel 31 and the third port of the seventh valve 7, and the control valve can control the on-off of the pipeline, so as to ensure that the reaction is performed in the reaction vessel 31;

a temperature control component (not shown in the drawings) for heating and/or cooling the reaction vessel, wherein the heating may be performed by an electric heating manner, and the cooling may be performed by an air cooling manner, which may specifically refer to the prior art and is not described herein again;

a third syringe 32 connected to the third port of the eighth valve 8, wherein the third syringe 32 contains a compound i precursor solution;

a second reagent container 33 connected to the third port of the ninth valve 9, wherein the second reagent container 33 is used for containing a TFA/DCM (trifluoroacetic acid/dichloromethane) solution;

a third reagent container 34 connected to the third port of the tenth valve 10, wherein the third reagent container 34 is used for containing an acetonitrile solution;

a fourth syringe 35 connected to the third port of the eleventh valve 11;

preferably, the seventh valve 7, the eighth valve 8, the ninth valve 9, the tenth valve 10, the eleventh valve 11 and the twelfth valve 12 are all electrically controlled valves (such as electromagnetic valves).

The structures of the seventh valve 7 to the twelfth valve 12, the third injector 32, the fourth injector 35, and the like in this embodiment have been described above, and are not described herein again.

The specific process of the reaction module for carrying out the reaction is shown in FIGS. 7(a) to 7(g),

initially, the seventh and eighth valves 7, 8 are in the condition shown in FIG. 7(a), where the pretreatment module is about to enrich¹⁸The F ions and the like enter the reaction vessel 31 (which may be a reaction flask, in particular) through the seventh valve 7.

Thereafter, as shown in fig. 7(b), the first valve 1 to the eighth valve 8 are in a state in which the first positive pressure line P1 outputs a positive pressure (inert gas input) to the reaction vessel 31, the second negative pressure line N2 is evacuated, the temperature control unit heats the reaction vessel 31 (for convenience of description, this step is collectively referred to as a "solvent removal step") to remove the solvent, and the heating temperature at this time is 80 to 130 ℃, whereby the activated reaction vessel can be obtained¹⁸And F ions.

Then, the seventh valve 7 and the eighth valve 8 are in the state shown in FIG. 7(c), the third syringe 32 pushes the precursor solution of the compound I (containing 1 to 10 mg of the precursor of the compound I in 0.2 to 2.0ml of acetonitrile) into the reaction vessel 31, and the mixture is heated to 90 to 140 ℃ under a sealed condition to react for 2 to 20 min, so that the precursor of the compound I and the K react¹⁸F/K₂₂₂Nucleophilic substitution reaction to produce compound I tert-butyl ester, followed by "solvent removal step".

Thereafter, the seventh to ninth valves 7 to 9 are in the state shown in fig. 7(d), and the third syringe 32 sucks the TFA/DCM solution in the second reagent container 33.

Then, the seventh valve 7 and the eighth valve 8 are in the state shown in fig. 7(c), the third injector 32 pushes a TFA/DCM solution (0.2-2.0 ml of 10-50% TFA/DCM solution) into the reaction vessel 31, and the reaction is performed at 30-100 ℃ for 1-30 min to remove the tert-butyl protecting group, so as to obtain a crude compound i, and after the reaction is completed, the "solvent removing step" is performed.

Thereafter, the tenth valve 10 to the eleventh valve 11 are in the state shown in fig. 7(e), and the fourth syringe 35 sucks the acetonitrile solution in the third reagent container 34.

Then, the seventh to eleventh valves 7 to 11 are in the state shown in fig. 7(f), the fourth syringe 35 pushes the acetonitrile solution into the reaction vessel 31 to dissolve the crude compound i, and then the fourth syringe 35 sucks the dissolved crude compound i solution again.

Finally, the eleventh to twelfth valves 11 to 12 are in the state shown in fig. 7(g), and the fourth syringe 35 pushes the dissolved crude compound i solution into the purification module.

In this embodiment, a specific reaction module is provided, and fluorine [ F ] is skillfully realized by the simple device through the change of the seventh valve 7 to the tenth valve 12 in different working states and the matching work of the first positive pressure pipeline P1, the second negative pressure pipeline N2, the reaction vessel 31 and the temperature control component¹⁸F]Nucleophilic substitution of mesyloxy in the precursor of compound I and tert-butyl ester of compound I. Especially, when the valves, the positive pressure pipeline, the negative pressure pipeline and the injector are automatically controlled, the automation of the two-step reaction can be realized.

In one embodiment, the reaction module further comprises:

a third linear drive (not shown in the drawings) capable of moving the piston of the third syringe 32 inside the hollow cylinder;

a fourth linear drive (not shown in the drawings) capable of moving the piston of the fourth syringe 35 inside the hollow cylinder;

further preferably, the third linear driving device and the fourth linear driving device are lead screws, and the lead screws are driven by stepping motors.

In this embodiment, the third and fourth linear drives are provided to control the third and

fourth injectors

32 and 35.

When the pneumatic rod and the hydraulic rod are used together with controllers such as a PLC (programmable logic controller), the automatic control of the third injector 32 and the fourth injector 35 can be conveniently realized.

The lead screw is used, the stroke of the pistons in the third injector 32 and the fourth injector 35 can be accurately controlled, and particularly when the lead screw is driven by a stepping motor, the lead screw is conveniently matched with controllers such as a PLC (programmable logic controller) and the like to realize automatic and accurate control of the third injector 32 and the fourth injector 35. The lead screw driven by the stepping motor can be assembled by self, and an electric push rod (a lead screw system) finished product can also be directly purchased.

In one embodiment, as shown in fig. 2, the purification module comprises:

a seventeenth valve 17, where the seventeenth valve 17 includes at least a first interface, a second interface, a third interface, a fourth interface, a fifth interface, and a sixth interface (corresponding to ((r) - (h) in fig. 5), respectively), where the seventeenth valve 17 is capable of switching between a first mode and a second mode, where the first mode is that the first interface is communicated with the second interface, the third interface is communicated with the fourth interface, and the fifth interface is communicated with the sixth interface; the second mode is that the second interface is communicated with the third interface, the fourth interface is communicated with the fifth interface, and the sixth interface is communicated with the first interface; a fourth port of the seventeenth valve 17 is connected with the reaction module (the third port of the twelfth valve 12) (the pipeline a is communicated with a pipeline a');

a chromatographic column assembly 36, wherein one end of the chromatographic column assembly 36 is connected with the second interface of the seventeenth valve 17;

a quantitative ring 37 (also called a sample feeding ring), wherein two ends of the quantitative ring 37 are respectively connected with the third interface of the seventeenth valve 17 and the sixth interface of the seventeenth valve 17;

a liquid delivery pump 38 connected to the first port of the seventeenth valve 17 for delivering a fluid (acetonitrile and water, in this embodiment, the ratio of acetonitrile/water = 6/1-3/1);

a second recovery tank 39 connected to the fifth port of the seventeenth valve 17;

the eighteenth valve 18, where the eighteenth valve 18 at least includes a first interface, a second interface, and a third interface, and the eighteenth valve 18 can enable the first interface to be communicated with the second interface or the first interface to be communicated with the third interface; the first port of the eighteenth valve 18 is connected to the other end of the chromatography column assembly 36, the second port of the eighteenth valve 18 is connected to the prescribing module (the third port of the twentieth valve 23), and the third port of the eighteenth valve 18 is connected to the second recovery vessel 39;

preferably, the seventeenth valve 17 and the eighteenth valve 18 are both electrically controlled valves.

First, as shown in fig. 5, a six-way valve is provided, which can perform the function of the seventeenth valve 17 described above.

Specifically, as shown in fig. 5(a) to 5(b), the six-way valve includes a six-way valve spool V4 having a circular cross section, and a six-way valve body V3 outside the six-way valve spool V4, and the six-way valve body V3 is provided with a first port (i), a second port (ii), a third port (iii), a fourth port (iv), a fifth port (V), and a sixth port (iv) in the counterclockwise direction. Through the rotary valve plug V4, the first port is communicated with the second port, the third port is communicated with the fourth port, the fifth port is communicated with the sixth port (as shown in fig. 5 (a)), or the second port is communicated with the third port, the fourth port is communicated with the fifth port, and the sixth port is communicated with the first port (as shown in fig. 5 (b)). In addition, given the above six-way valve structure, those skilled in the art know how to control the six-way valve spool V4 to rotate relative to the six-way valve body V3 by a fixed angle to achieve electric (electromagnetic) control of the six-way valve (e.g., set the stepper motor control spool V4 to rotate).

In addition, as shown in fig. 2(a) and 2(b), the eighteenth valve 18 is a three-way valve which can realize the communication between the first port (r) and the second port (r) or the communication between the first port (r) and the third port (r), and is a prior art, and a corresponding electrically-operated control valve (e.g., an electromagnetic valve) can be directly purchased in the market.

Chromatography columns are prior art and will not be described in detail here. The column assembly 36 of the present application is an existing column or a combination of columns (e.g., a plurality of columns in series and/or parallel).

The specific process of purification by the purification module can be as shown in FIG. 2(a) and FIG. 2(b),

at the beginning, the seventeenth valve 17 is in the state shown in fig. 2(a), at this time, the solution dissolving the crude compound i flowing from the reaction module enters the quantitative loop 37 through the fourth port r and the third port r, and a small amount of the redundant solution flows into the second recovery container 39 through the sixth port c and the fifth port c, at this time, the solution dissolving the crude compound i remains in the quantitative loop 37.

Then, the seventeenth valve 17 is in the state shown in fig. 2(b), and the eighteenth valve 18 opens the first port and the third port, and at this time, the liquid feed pump 38 starts to operate. The liquid transfer pump 38 pushes out the fluid (acetonitrile and water), and the fluid flows through the first port and the sixth port, then carries out purification by taking out the solution dissolving the crude compound I in the quantitative ring 37 and flowing into the chromatographic column assembly 36 through the third port and the second port.

Finally, the eighteenth valve 18 connects the first port and the second port, and the purified solution of compound i is pushed into the prescription module by the fluid pushed out by the liquid delivery pump 38.

In this embodiment, a specific purification module is provided, and the seventeenth valve 17 and the eighteenth valve 18 are changed in different working states and cooperate with the liquid transfer pump 38 to purify the crude compound i to obtain the pure compound i. In particular, when the valves, the positive pressure line, and the liquid feed pump 38 are automatically controlled, the above-described automation of purification can be realized.

In one embodiment, the prescribing module includes:

a thirteenth valve 13, a fourteenth valve 14, a fifteenth valve 15, a sixteenth valve 16, a nineteenth valve 19, a twentieth valve 20, a twenty-first valve 21, a twentieth valve 22, and a twentieth valve 23, wherein the thirteenth valve 13 to the sixteenth valve 16 and the nineteenth valve 19 to the twentieth valve 23 respectively comprise at least a first interface, a second interface, and a third interface, and the thirteenth valve 13 to the sixteenth valve 16 and the nineteenth valve 19 to the twentieth valve 23 are all capable of conducting any two of the three interfaces or none of the three interfaces; wherein the first port of the tenth valve 13 is connected to the second port of the tenth valve 12, the second port of the tenth valve 13 is connected to the first port of the fourteenth valve 14, the second port of the fourteenth valve 14 is connected to the first port of the fifteenth valve 15, the second port of the fifteenth valve 15 is connected to the first port of the sixteenth valve 16, the second port of the sixteenth valve 16 is connected to the first port of the nineteenth valve 19, the second port of the nineteenth valve 19 is connected to the first port of the twentieth valve 20, the second port of the twentieth valve 20 is connected to the first port of the twenty-first valve 21, the second port of the twenty-first valve 21 is connected to the first port of the twenty-second valve 22, and the second port of the twenty-second valve 22 is connected to the first port of the twenty-third valve 23, the second port of the twentieth valve 23 is connected to a fourth negative pressure line N4, and the third port of the twentieth valve 23 is connected to the purification module (the second port of the eighteenth valve 18) (the line B is communicated to the line B');

a fifth syringe 40 connected to the third port of the thirteenth valve 13;

a fourth reagent container 41 connected to the third port of the fourteenth valve 14, wherein the fourth reagent container 41 is configured to contain absolute ethanol;

a fifth reagent container 42 connected to the third port of the fifteenth valve 15, wherein the fifth reagent container 42 is used for containing a sodium chloride solution;

a sixth reagent container 43 connected to the third port of the sixteenth valve 16, wherein the sixth reagent container 43 is used for containing water;

a first relay tank 44 connected to the third port of the nineteenth valve 19;

a second transfer container 45 connected to the third port of the twentieth valve 22 and the third negative pressure line N3, respectively, wherein the second transfer container 45 is used for containing auxiliary materials (polysorbate 80 (II), vitamin C, sodium chloride injection, and sterile water for injection);

a compound i enrichment bin 46 connected between the third port of the twentieth valve 20 and the third port of the twenty-first valve 21, wherein octadecyl bonded silica gel is filled in the compound i enrichment bin 46;

and a finished product collecting container 47 connected to the second transfer container 45.

The structures of the thirteenth to sixteenth valves 13 to 16 and the nineteenth to twentieth valves 23, the fifth injector 40, and the like in this embodiment have been described above and will not be described again.

The specific process of enriching and prescribing by the prescribing module is shown in FIGS. 8(a) -8 (g),

at the beginning, the nineteenth to twentieth valves 19 to 23 are in the state shown in FIG. 8(a), and at this time, the compound I product solution flowing out of the purification module enters the first transfer container 44.

Thereafter, as shown in fig. 8(b), the thirteenth to sixteenth valves 13 to 16 are in the state, and at this time, the fifth syringe 40 extracts the sterile water for injection stored in the sixth reagent container 43.

Then, the thirteenth to sixteenth valves 13 to 16 and the nineteenth valve 19 are in the state shown in fig. 8(c), and at this time, the fifth syringe 40 pushes the sterilized water for injection into the first relay container 44 to dilute the compound i product solution, and then the fifth syringe 40 draws the compound i product solution into the fifth syringe 40.

Thereafter, the thirteenth to sixteenth valves 13 to 16 and the nineteenth to twentieth valves 23 are in the condition shown in fig. 8(d), at which time the fifth syringe 40 pushes out the compound i product solution to start the enrichment in the compound i enrichment bin 46.

Thereafter, the thirteenth to sixteenth valves 13 to 16 and the nineteenth to twentieth valves 23 are in the state shown in fig. 8(d), and at this time, the fifth syringe 40 pushes the sterilized water for injection to flush the compound i enrichment silo 46, thereby further enriching.

Thereafter, the thirteenth to fourteenth valves 13 to 14 are in the state shown in fig. 8(e), and the fifth syringe 40 draws the absolute ethanol contained in the fourth reagent container 41.

Thereafter, the thirteenth to sixteenth valves 13 to 16 and the nineteenth to twentieth valves 23 are in the same state as that of fig. 8(f), and at this time, the fifth syringe 40 pushes out the absolute ethanol, and the third negative pressure line N3 is evacuated, so that the pure compound i enriched in the enrichment bin 46 is eluted into the second transfer container 45.

Thereafter, the thirteenth to fifteenth valves 13 to 15 are in the state shown in fig. 8(g), and the fifth syringe 40 draws the sodium chloride solution contained in the fifth reagent container 42.

Thereafter, the thirteenth to sixteenth valves 13 to 16 and the nineteenth to twentieth valves 19 to 23 are in the state shown in fig. 8(f), at which time the fifth syringe 40 pushes out the sodium chloride solution and the third negative pressure line N3 is evacuated, thereby eluting the pure compound i enriched in the enrichment bin 46 to the second transfer container 45 again.

Finally, referring to fig. 8(h), the first valve 1 to the sixteenth valve 16, the nineteenth valve 19 to the twenty-first valve 21 are all communicated with the first port and the second port, the twentieth valve 22 is communicated with the first port and the third port, the first positive pressure pipeline P1 provides positive pressure (and the third negative pressure pipeline N3 is closed), so that the mixed solution in the second transfer container 45 is pushed into the finished product collection container 47, and the final compound i liquid composition is collected. Preferably, a filter (e.g., a needle filter) is disposed between the second transfer container 45 and the finished product collection container 47, so that the compound i solution flowing out of the second transfer container 45 is filter sterilized to be collected in the finished product collection container 47 to obtain a finished product.

In one embodiment, the prescribing module further includes:

a fifth linear drive (not shown in the drawings) capable of moving the piston of the fifth syringe 40 inside the hollow cylinder;

When the pneumatic rod and the hydraulic rod are used for matching with controllers such as a PLC and the like, the automatic control of the fifth injector 40 is conveniently realized.

The lead screw is used, so that the stroke of the piston in the fifth injector 40 can be accurately controlled, and particularly, when the lead screw is driven by the stepping motor, the lead screw is conveniently matched with controllers such as a PLC (programmable logic controller) and the like to realize automatic and accurate control of the fifth injector 40. The lead screw driven by the stepping motor can be assembled by the user, and an electric push rod (a lead screw system) finished product can be directly purchased.

In addition, in the above technical solution, a detection/monitoring device is provided to detect the operation of the device. In particular, can be in pairs¹⁸Radioactivity detectors are disposed at one or more positions of the F ion enrichment bin 27, the third reagent container 34, the line between the twelfth valve 12 and the seventeenth valve 17, and the compound i enrichment bin 46 to detect radioactivity. An ultraviolet detector and a radioactivity detector can be arranged on the chromatographic column assembly to judge whether the control starts to collect the purified mobile phase.

This example provides a process for producing a liquid composition of compound i using the apparatus described above, comprising:

enrichment using a pre-processing module¹⁸F ions;

enriching using reaction modules¹⁸Reacting F ions with a precursor of the compound I to generate a tert-butyl ester of the compound I, and performing a tert-butyl esterification reaction on the tert-butyl ester of the compound I to obtain a crude product of the compound I;

and (3) formulating the purified compound I pure product by using a formulation module to obtain the compound I liquid composition. More specific operation steps have been described above and will not be described further.

While embodiments of the present application have been described above, the present application is not limited to the specific embodiments and applications described above, which are intended to be illustrative, instructive, and not limiting. Those skilled in the art, having the benefit of this disclosure, may effect numerous modifications thereto and changes may be made without departing from the scope of the invention as defined by the appended claims.

Claims

1. An apparatus for producing a compound I liquid composition, comprising:

a pre-processing module for enriching¹⁸F ions;

reaction module for enriched¹⁸Reacting the F ions with a precursor of the compound I to generate a tert-butyl ester of the compound I, and performing a tert-butylation reaction on the tert-butyl ester of the compound I to obtain a crude product of the compound I;

the prescription module is used for enriching and prescribing the purified compound I pure product into a compound I liquid composition;

a compound I.

2. The apparatus of claim 1,

the preprocessing module comprises:

the first valve to the sixth valve respectively comprise at least a first interface, a second interface and a third interface, and any two interfaces of the three interfaces can be conducted or none of the three interfaces can be conducted by the first valve to the sixth valve; the first interface of the first valve is connected with a first positive pressure pipeline, the second interface of the first valve is connected with the first interface of the second valve, the second interface of the second valve is connected with the first interface of the third valve, the second interface of the third valve is connected with the first interface of the fourth valve, the second interface of the fourth valve is connected with the first interface of the fifth valve, and the second interface of the fifth valve is connected with the first interface of the sixth valve;

a first reagent container connected to the third port of the second valve;

a first injector connected to a third port of the third valve;

and the second injector is connected with the third interface of the sixth valve.

3. The apparatus of claim 2,

the pre-processing module further comprises:

and the second linear driving device can drive the piston of the second injector to move in the hollow cylinder.

4. The apparatus of claim 2,

the pre-processing module further comprises:

the positive pressure negative pressure pipeline and the liquid adding pipeline respectively penetrate through the piston of the second injector and extend into the second injector.

5. The apparatus of claim 2,

the reaction module includes:

a third syringe connected to the third port of the eighth valve;

a second reagent container connected to the third port of the ninth valve;

a third reagent container connected to the third port of the tenth valve;

a fourth syringe connected to the third port of the eleventh valve.

6. The apparatus of claim 5,

the reaction module further comprises:

and the fourth linear driving device can drive the piston of the fourth syringe to move in the hollow cylinder.

7. The apparatus of claim 5,

the purification module comprises:

a chromatographic column assembly, one end of which is connected with the second interface of the seventeenth valve;

the liquid conveying pump is connected with a first interface of the seventeenth valve;

the eighteenth valve at least comprises a first interface, a second interface and a third interface, and the eighteenth valve can realize the conduction of the first interface and the second interface or the conduction of the first interface and the third interface; and the first interface of the eighteenth valve is connected with the other end of the chromatographic column assembly, the second interface of the eighteenth valve is connected with the prescription module, and the third interface of the eighteenth valve is connected with the second recovery container.

8. The apparatus of claim 7,

the prescribing module includes:

a fifth injector connected to the third port of the thirteenth valve;

a fourth reagent container connected to the third port of the fourteenth valve;

a fifth reagent container connected to the third port of the fifteenth valve;

a sixth reagent container connected to the third port of the sixteenth valve;

9. The apparatus of claim 8,

the prescribing module further comprises:

and the fifth linear driving device can drive the piston of the fifth syringe to move in the hollow cylinder.

10. A process for producing a liquid composition of compound i using the apparatus of any one of claims 1 to 9, comprising:

enrichment using a pre-processing module¹⁸F ions;

using reaction modules for enrichment¹⁸Reacting F ions with a precursor of the compound I to generate a compound I tert-butyl ester, and performing a tert-butyl esterification reaction on the compound I tert-butyl ester to obtain a crude product of the compound I;

11. Use of the apparatus of any one of claims 1 to 9 for the production of a liquid composition of compound i.