CN114950304A

CN114950304A - Skid-mounted equipment and method for preparing 2-methacryloyloxyethyl phosphorylcholine

Info

Publication number: CN114950304A
Application number: CN202210700250.0A
Authority: CN
Inventors: 张惠
Original assignee: Individual
Current assignee: Individual
Priority date: 2022-06-20
Filing date: 2022-06-20
Publication date: 2022-08-30
Anticipated expiration: 2042-06-20
Also published as: CN114950304B

Abstract

The invention provides skid-mounted equipment and a method for preparing 2-methacryloyloxyethyl phosphorylcholine, which are characterized in that 2-chloro-2-oxo-1, 3, 2-dioxaphospholane (COP) is synthesized on line through a primary microchannel reactor, 2-alkyl-2-oxo-1, 3, 2-dioxaphospholane (OPEMA) is prepared through a secondary microchannel reactor by taking the COP as a reactant, and 2-Methacryloyloxyethyl Phosphorylcholine (MPC) is prepared through a tertiary microchannel reactor by taking the OPEMA as a reactant; separating and recycling low-boiling point reactants and solvents in the MPC product by a scraper film reduced pressure distillation process; and transferring the concentrated MPC into a vacuum rake type all-in-one dryer for low-temperature melting crystallization purification, filtering and draining liquid, and drying at low temperature and high vacuum to obtain the refined MPC product. The invention reduces side reaction, simplifies steps, improves yield, and has the productivity 51 times that of the traditional process.

Description

Skid-mounted equipment and method for preparing 2-methacryloyloxyethyl phosphorylcholine

Technical Field

The invention belongs to the technical field of chemical equipment manufacturing and organic synthesis, relates to a method for preparing 2-methacryloyloxyethyl phosphorylcholine, and particularly relates to skid-mounted equipment and a skid-mounted method for preparing 2-methacryloyloxyethyl phosphorylcholine by three-stage microchannel reaction-crystallization filtration-vacuum drying coupling.

Background

2-methacryloyloxyethyl phosphorylcholine (2-methacryloyloxyethyl phosphorylcholine, MPC, CAS No.: 67881-98-5) is an important pharmaceutical intermediate compound. Ishihara et al in Japan, 1990, reported that they successfully synthesized a phosphorylcholine monomer, 2-Methacryloyloxyethyl Phosphorylcholine (MPC), which possessed both a methacrylic acid structure and a phosphorylcholine end group. Since then, studies based on the synthesis of MPC polymers and in the modification of surface functions have been developed. In-vivo and in-vitro experiments prove that the bionic surface prepared by the polymer can effectively simulate the structure of a natural cell membrane, and the phosphorylcholine group of the bionic surface plays an excellent biocompatibility role when contacting with body fluid components such as protein, platelet and the like, thereby effectively reducing the adsorption of the protein and the adhesion of the platelet. Introduction of phospholipids such as phosphatidylcholine into polymers to construct polymers similar to phospholipid molecules in biological tissues to obtain materials with high biocompatibility has attracted great attention in the biomedical field. 2- (methacryloyloxy) ethyl-2- (trimethylamino) ethyl phosphate (MPC), i.e., an acrylate containing phosphatidylcholine groups, synthesized by Tadao Nakaya of Japanese and copolymers thereof exhibit excellent anticoagulant properties, protein adsorption reducing and protein denaturation reducing properties (Toshikazu Yoneyama, Ken-ichi Sug ihara, Kazuhiko Ishihara, Yasuhiko Iwasaki, Nobuo Nakabayashi. biomaterials 23(2002)1455 and 1459), but none of these materials have degradability. For introducing phosphatidylcholine groups into degradable polyester molecules to improve the biocompatibility of materials, Nakabayashi et al performed preliminary research in 2003 (Yasuhiko Iwasaki, Yoko Tojo, Tomoyuki Kurosaki, Nobuo Nakabayashi.J Biomed Mater Res,2003,65A: 164. 169), they initiated lactide ring-opening polymerization with Glycerophosphorylcholine (L-a-glycophosphostyrylchlorine) to obtain polylactic acid molecules with only one phosphatidylcholine in the side chain; hilborn et al obtained polycaprolactone containing a phosphatidylcholine group at one end by reacting the end group on one side of polycaprolactone with 2-chloro-2-oxo-1, 3, 2-dioxolane and opening the ring with trimethylamine (Fredrk Nederberg, Tim Bowden, and joints Hilborn. macromolecules2004,37, 954-. In China, Bencheng et al, in the 'phosphatide biodegradable polyester and preparation method thereof' with the patent application number of 200410093122.6, disclose that a phosphatidylcholine group is introduced into the end group of polyester and the preparation method thereof. However, the phosphatidylcholine groups introduced in these publications or patents have a limited number in the polymer chain of the polyester and thus have limited contribution to the properties of the overall material, and different materials having good biocompatibility that meet the requirements of different drug controlled release and tissue engineering cannot be obtained.

From the above, MPC is known to play an important role in the bioaffinity material industry. The conventional production process flow of 2-Methacryloyloxyethyl Phosphorylcholine (MPC) at present comprises condensation cyclization reaction, oxidation reaction, esterification reaction, amination ring-opening reaction and various purification and post-treatment processes, and has the disadvantages of numerous used equipment, complex production process, high energy consumption, low product yield and environmental protection. The following problems associated with conventional processes (FIG. 2) are specifically described below:

1. cyclized condensation reaction

Carrying out condensation reaction on phosphorus trichloride and ethylene glycol in a reaction kettle to obtain phosphorous oxychloride CUP, wherein the conversion rate in the process is about 70%; a large amount of hydrogen chloride is generated in the synthesis process, and the waste gas is neutralized by a designed closed spraying system. The process conventionally uses a 500L-1000L reaction kettle for dropwise adding reaction, and has the disadvantages of long reaction time, difficult temperature control, high energy consumption, more byproducts and serious potential safety hazard if the reaction temperature is not controlled well in the production process because the specific surface area of the reaction kettle is obviously reduced, the reaction heat transfer area is small, the kettle type reaction heat transfer effect is poor, and the reaction conversion rate is low.

PCl ₃ +C ₂ H ₆ O ₂ ＝2HCl+C ₂ H ₄ ClO ₂ P

2. Oxidation reaction

Performing gas-liquid oxidation reaction on the product CUP of the previous step and dry oxygen in a traditional reaction kettle to obtain a product COP, wherein the process is a gas-liquid two-phase reaction, and the height-diameter ratio of the traditional reaction kettle is less than 2: 1, the residence time of gas in a reactor is very short, so that the conversion efficiency of gas-liquid two-phase reaction is quite low, the reaction time has to be prolonged to improve the conversion rate, therefore, the reaction period is as long as 72-144 h, in order to improve the reaction rate, the reactor needs to be heated and heated, the energy consumption is high, and certain potential safety hazard is caused, even under such conditions, the conversion rate of the reaction in the step is only 50%, and the post-treatment purification process needs molecular distillation equipment, needs high vacuum operation, has very high corrosivity of materials, has harsh requirements on the equipment, and because COP has heat sensitivity, in the COP purification process, due to long-time heating, COP has the risk of denaturation and even implosion explosion, so that the purification link has great potential safety hazard.

2C ₂ H ₄ ClO ₂ P+O ₂ ＝2C ₂ H ₄ ClO ₃ P

3. Esterification reaction

In a system with acetonitrile as a solvent in a traditional reaction kettle, triethylamine as a catalyst and HEMA as a reactant are added, and the reaction product COP obtained in the previous step is dropwise added into the system to carry out esterification reaction to obtain a product OPEMA, wherein the conversion rate in the step is about 90%. Because the reaction conversion rate of the kettle type process is very low, in order to improve the conversion rate, a catalyst such as triethylamine and the like is generally added in the reaction, the addition of the catalyst can promote the reaction to be converted towards the positive reaction direction, but the reaction is more severe and a large amount of heat is emitted after the catalyst is added, if the temperature of the reaction kettle is not well controlled, the local high temperature of the reaction can be caused, and the material is denatured and deteriorated, so a large amount of solvent is needed for dilution and temperature control, and the slow dripping is needed, so that the reaction period is longer, and the energy consumption is very large. In addition, a large amount of solid salt is generated in the step, post-treatment such as filtration, concentration and purification is needed, the process is complex, the material loss is large, and the process pollution is serious.

4. Ring opening amination reaction

In a high-pressure reaction kettle, acetonitrile is used as a solvent, the product OPEMA in the previous step is added, then trimethylamine is used as a ring-opening agent to carry out an amine addition reaction, the conversion rate in the step is about 50 percent, excessive unreacted material trimethylamine is condensed and captured by a pipeline ultralow temperature condensation recycling system (-10 to-15 ℃), and then the excessive unreacted material trimethylamine is refluxed to a feeding system for reuse. The reaction conversion rate is low, the energy consumption is high, and the environmental-friendly aftertreatment pressure is large.

5. Post-treatment process

Under the low-temperature environment, MPC is crystallized and precipitated from a solution system, and then is subjected to the treatment steps of filtering, washing, decoloring, drying and the like, the post-treatment process is complicated, the material loss and deformation are easily caused, the requirements on operating equipment and environment are harsh, the yield is low, and the conversion rate in the step is about 50%.

The traditional kettle type reactor belongs to a conventional kettle type dripping process, and because the specific surface area of the reaction kettle is obviously reduced, the reaction heat transfer area is small, the kettle type reaction heat transfer effect is poor, the heat generation and heat removal imbalance is easily caused, the heat accumulation is generated, the temperature in the reaction kettle is rapidly increased, the chemical reaction is further accelerated, and the reaction is out of control and even explodes. Therefore, the traditional kettle type process reaction needs a large amount of solvent to dilute materials so as to control the reaction to slowly proceed, a large amount of heat is released in the synthesis reaction process of CUP, COP and OPEMA, the kettle type reaction needs to strictly control low temperature to ensure controllable and safe reaction, and slow dropwise addition reaction is performed.

In addition, the yield of CUP and COP synthesized by the traditional kettle type reaction process is low, and the CUP and COP contain a plurality of byproducts, so that the CUP and COP need to be purified. But also has a plurality of problems in the purification process, the cyclic chlorophosphate has higher boiling point, belongs to a heat-sensitive material, has strong corrosivity, is not easy to be quickly evaporated out in the vacuum distillation process, and has higher requirement on purification equipment. There is also a risk that cyclic chlorophosphate is denatured or polymerized by long-term heating during the post-treatment process and even explosion occurs during the purification process.

Also, the researchers have conducted new process research by using methylene chloride as solvent and phosphorus oxychloride and ethylene glycol to perform substitution cyclization reaction in a kettle reactor

Theoretically, phosphorus oxychloride has three very active phosphorus-chlorine bonds, the phosphorus-chlorine bonds can perform substitution reaction with two hydroxyl groups of ethylene glycol, and intramolecular ring formation reaction is preferentially performed to generate COP, but the COP has one active phosphorus-chlorine bond, and can still perform substitution reaction with the hydroxyl groups in the system to generate byproducts, so that gelation is realized. This side reaction is not addressed by removing the heat of reaction, which occurs because of the reaction that occurs as a result of the constant contact of the COP with the hydroxyl-containing material. If the COP product generated by the reaction can be quickly removed, the generation of side reaction can be avoided, but the conventional kettle type reaction process needs to prolong the contact reaction time of materials because of low heat exchange efficiency, limited stirring speed and poor mixing effect, so that the COP product generated firstly and the reactant ethylene glycol are mixed together to continue the side reaction, and the yield of the COP in the synthesis process taking phosphorus oxychloride as the reactant is low or even the reaction fails. The problems lead the process period for synthesizing the MPC to be very long, generally about 7 days, and lead the yield to be very low, the energy consumption to be large, the pressure for purifying the subsequent products to be large, the burden of environmental protection to be heavy and the manufacturing cost of the MPC to be very high. Therefore, the development of a new process capable of rapidly and efficiently synthesizing 2-methacryloyloxyethyl phosphorylcholine is urgently needed, so that the cost is saved, the energy consumption is reduced, and the reaction conversion rate and the yield are improved.

Disclosure of Invention

In order to overcome the defects of the prior art, the invention aims to provide skid-mounted equipment and a skid-mounted method for preparing 2-methacryloyloxyethyl phosphorylcholine by coupling three-stage microchannel reaction-crystallization filtration-vacuum drying, and the rapid conversion of multi-step reaction is realized by the microchannel reactor technology. The microchannel reactor technology is a technology for manipulating and treating a chemical reaction with an extremely small amount of liquid using channels of several tens to hundreds of micrometers. The micro structure in the micro-channel reactor ensures that the micro-reactor equipment has extremely large specific surface area which can be hundreds of times or even thousands of times of the specific surface area of a stirring kettle, so that the micro-channel reactor has extremely good heat transfer and mass transfer capacity, and can realize instant uniform mixing and efficient heat transfer of materials; the synthesis process of the OPEMA can exchange heat efficiently, and the microchannel reactor can quickly remove huge heat emitted in the esterification reaction process, thereby avoiding the deterioration and the denaturation of products and greatly accelerating the reaction rate; in the MPC reaction process, the microchannel reactor is utilized to change the gas-liquid reaction mode of the traditional kettle type process, a liquid-liquid reaction system is used, an organic solvent system of trimethylamine is used to replace gaseous trimethylamine in the traditional process, the trimethylamine in a liquid phase system and the OPEMA in a liquid state are synchronously subjected to liquid-liquid reaction in the third-stage microchannel reactor, the reaction rate is greatly improved, the reaction conversion rate is improved, the MPC synthesis period is changed from 18 hours of the traditional process to 3 minutes, and the yield is 99%. The following three-step reaction process is carried out in a three-stage microchannel reactor:

reaction in the first stage microchannel reactor:

phosphorus oxychloride and ethylene glycol continuously flow in a first-stage microchannel reactor to quickly perform a substitution cyclization reaction, and the reaction temperature is increased to accelerate the reaction rate, so that the reaction is quickly finished, the generated product COP does not flow back, the phenomenon that the COP and the ethylene glycol contact to generate a side reaction to generate a gel substance in the conventional kettle type process is avoided, the temperature in the reaction process in the microchannel reactor can be accurately controlled, other chemical solvents are not used in the reaction process, the purity of the generated product COP is high, and the product COP can be directly used for the synthesis of OPEMA in the next step;

reaction in the second stage microchannel reactor:

products COP and HEMA of a previous stage microchannel reactor are directly subjected to esterification reaction in the microchannel reactor under the solvent-free condition, a large amount of heat is released in the esterification reaction process, in order to ensure normal reaction, the traditional kettle type dripping process needs to be strictly controlled at low temperature (-20 ℃ to-30 ℃), triethylamine is also needed to be added as a catalyst in a system taking acetonitrile as a solvent, the catalyst is added to promote the reaction to be converted to the positive reaction direction, but the reaction is more severe and a large amount of heat is released after the catalyst is added, if the temperature of the reaction kettle is not well controlled, the local high temperature of the reaction can cause material degeneration and deterioration, so a large amount of solvent is needed to dilute and control the temperature, and the slow dripping is needed, so that the reaction period is longer, the reaction rate is 1kg/1000min, and the energy consumption is very high. This step produces a large amount of solid salt, and needs post-treatment such as filtration, concentration and purification, and the technology is comparatively complicated, and the material loss is great, and the process is polluted seriously. In the traditional process, a large amount of solid salt is generated, a microchannel reactor is blocked, and the preparation of the conventional process cannot be carried out by using a microchannel. Based on this, the invention designs that COP and HEMA are directly carried out esterification reaction in a microchannel reactor under the condition of no solvent and no catalyst, the micro structure in the microchannel reactor enables the microreactor equipment to have a very large specific surface area which can be hundreds of times or thousands of times of the specific surface area of a stirring kettle, so that the microreactor has excellent heat transfer and mass transfer capabilities, and can realize instant uniform mixing and efficient heat transfer of materials, thereby improving the reaction temperature and increasing the reaction rate, and efficiently synthesizing OPEMA under the condition of no catalyst, wherein the reaction rate is 1kg/2min which is 500 times of the kettle type reaction rate.

Reaction in the third stage microchannel reactor:

in the MPC reaction process, the microchannel reactor is utilized to change the gas-liquid reaction mode of the traditional kettle type process, a liquid-liquid reaction system is used, an organic solvent system of trimethylamine is used to replace gaseous trimethylamine in the traditional process, the trimethylamine in a liquid phase system and the OPEMA in a liquid state are synchronously subjected to liquid-liquid reaction in the third-stage microchannel reactor, the reaction rate is greatly improved, the reaction conversion rate is improved, the MPC synthesis period is shortened to 3min from 18h of the traditional process, and the yield is 99%.

After material synthesis is carried out in a three-stage microchannel reactor, reactants are transferred to a time delay reaction kettle for concentration, and the materials are quickly crystallized and dried in a vacuum rake type all-in-one dryer to obtain the product 2-methacryloyloxyethyl phosphorylcholine with the purity of 99.5%.

The skid-mounted equipment and the skid-mounted method can realize continuous operation, greatly reduce the potential safety hazard of fine chemical engineering in research, development and production, effectively improve the chemical reaction rate and the operation safety, and have the advantages of small characteristic size, large specific surface area, laminar flow flowing behavior, accurately controllable residence time, high heat and mass transfer efficiency, no amplification effect, small occupied area and the like.

Based on the above description, the skid-mounted equipment for preparing 2-methacryloyloxyethyl phosphorylcholine provided by the invention comprises a skid-mounted equipment main body consisting of three stages of microchannel reactors, a time delay reaction kettle, a vacuum rake type all-in-one dryer, an exhaust fan, a tail gas treatment system, a tube array condenser, a vacuum pump set and a material recovery tank, and comprises a PLC (programmable logic controller) for controlling the system; the skid-mounted equipment main body consisting of each stage of microchannel reactor comprises a material storage tank, the microchannel reactor, a plunger metering pump and a mass flow meter, wherein the material storage tank is connected with the microchannel reactor; a feed inlet of the delay reaction kettle is connected with a third-stage microchannel reactor of the skid-mounted equipment main body, a discharge outlet of the delay reaction kettle is respectively connected with a tube nest condenser and a vacuum rake type all-in-one dryer, and a material recovery tank is connected with the tube nest condenser; the vacuum pump set is communicated with the delay reaction kettle and the vacuum rake type all-in-one dryer through the tube nest condenser, and is used for vacuumizing the delay reaction kettle and the vacuum rake type all-in-one dryer.

Furthermore, the skid-mounted reaction system is arranged in a four-layer frame structure, the frame structure is provided with stairs, and a nitrogen interface and a high-low temperature medium interface are reserved on each layer of the frame structure.

The method for preparing 2-methacryloyloxyethyl phosphorylcholine provided by the invention is realized by the skid-mounted equipment, and comprises the following steps:

introducing pure phosphorus oxychloride in a first storage tank and anhydrous ethylene glycol in a second storage tank into a microchannel mixer arranged in a first microchannel reactor by using a first plunger metering pump and a second plunger metering pump, mixing, then entering the first microchannel reactor for rapid substitution cyclization reaction, introducing the effluent of the first microchannel reactor into a first cyclone gas-liquid separator to separate a gaseous product and a liquid product COP generated by the reaction, and directly transferring the generated liquid product COP into a third liquid storage tank of a second microchannel reactor; an exhaust port of the first cyclone gas-liquid separator is communicated with an exhaust fan and a tail gas treatment system;

(II) introducing COP in the third storage tank and anhydrous hydroxyethyl methacrylate HEMA in the fourth storage tank into a microchannel mixer arranged in a second microchannel reactor by using a third plunger metering pump 23 and a fourth plunger metering pump, mixing, then introducing the mixture into the second microchannel reactor for rapid esterification, introducing the effluent of the second microchannel reactor into a second cyclone gas-liquid separator for separating a gaseous product and a liquid product OPEMA generated by the reaction, and directly transferring the generated liquid product OPEMA into a fifth liquid storage tank of a third-stage microchannel reactor; an exhaust port of the second cyclone gas-liquid separator is communicated with an exhaust fan and a tail gas treatment system;

introducing OPEMA in the fifth storage tank and trimethylamine organic solution TMA in the sixth storage tank into a microchannel mixer arranged in a third microchannel reactor by using a fifth plunger metering pump and a sixth plunger metering pump, mixing, then entering the third microchannel reactor for rapid amination ring-opening reaction, and entering a crude MPC solution discharged from the third microchannel reactor into a time-delay reaction kettle;

fourthly, pumping the reactant TMA with low boiling point in the 2-methacryloyloxyethyl phosphorylcholine product and the solvent into a tubular condenser in a gaseous form through vacuum distillation of a scraper film on the crude material MPC solution in the time delay reaction kettle by a vacuum pump set, carrying out heat exchange condensation to obtain a mixed solution, and collecting and recycling the mixed solution by a material recovery tank; and directly transferring the concentrated 2-methacryloyloxyethyl phosphorylcholine crude product mixed solution into a vacuum rake type all-in-one dryer for low-temperature melting crystallization purification, filtering and draining liquid, and then performing high-vacuum drying under the low-temperature condition to obtain a refined grade 2-methacryloyloxyethyl phosphorylcholine product.

Preferably, each stage of the microchannel reactor comprises a microchannel mixer arranged on the microchannel reactor, the liquid holdup of the microchannel mixer is 100mL, and the characteristic dimension of a channel is 200 micrometers; the microchannel reactor is made of Hastelloy, has the characteristic dimension of 200 micrometers, the liquid holdup of 2000mL and the heat exchange capacity per unit volume of 33MW per square meter K, is provided with an online temperature and pressure detection system, and is provided with a temperature control interface which can be connected with a high-low temperature medium interface in a quick-assembly manner;

preferably, the molar ratio of phosphorus oxychloride to ethylene glycol in step (one) is: 1.05: 1; controlling the temperature of the first microchannel reactor and the microchannel mixer to be 0-25 ℃; the flow rate of the first plunger metering pump is 0-60.0L/h, and the flow rate of the second plunger metering pump is 0-34.4L/h;

preferably, the second microchannel reactor and the microchannel mixer described in step (two) are controlled to have a temperature of 45 to 65 ℃; the flow rate of the third plunger metering pump is 0-60.0L/h, and the flow rate of the fourth plunger metering pump is 0-74.7L/h;

preferably, the third microchannel reactor and microchannel mixer described in step (III) are controlled to a temperature of 60-75 ℃; the flow rate of the fifth plunger metering pump is 0-45.0L/h, and the flow rate of the sixth plunger metering pump is 0-90.0L/h; the trimethylamine organic solution (TMA) is preferably a trimethylamine acetonitrile solution and a trimethylamine tetrahydrofuran solution, wherein the trimethylamine accounts for 30% by mass;

preferably, the volume of the time-delay reaction kettle is 200L, and the time-delay reaction kettle is a double-layer jacket reaction kettle and is provided with a high-speed stirring motor and a stirring paddle, wherein the stirring paddle in the kettle is of a scraper type, and the scraper is made of polytetrafluoroethylene and is 20mm away from the inner wall of the reaction kettle; the delay reaction kettle is provided with a weighing module and a liquid level meter, the mass and the volume of materials in the storage tank can be accurately measured, the storage tank is provided with a feed valve, a discharge valve, a vacuum pumping valve, a nitrogen interface and a vacuum pressure gauge, and the discharge valve at the bottom of the storage tank is a temperature measurement discharge valve;

preferably, the delayed reaction kettle reaction conditions are: controlling the temperature to 65 ℃, pressurizing the nitrogen by 0.4Mpa, stirring at the speed of 400rpm, and reacting for 3 h;

preferably, the delayed reaction kettle concentration conditions are: controlling the temperature to 65 ℃, the absolute pressure to 1000pa and the processing time to 1 h;

preferably, the heat exchange area of the shell and tube condenser is 1 square meter, and the temperature is controlled to be-40 ℃;

preferably, the vacuum pump set is a three-stage Roots vacuum pump set, the ultimate vacuum is 0.01pa, the air suction amount is 200L/s, and an air outlet of the vacuum pump set is connected with an exhaust fan-tail gas treatment system;

preferably, the vacuum rake type all-in-one dryer is of a spherical structure, the effective volume of the vacuum single-arm rake type dryer is 150L, and the vacuum rake type all-in-one dryer is provided with a jacket temperature control layer communicated with the high-low temperature medium interface; the vacuum rake type all-in-one dryer is provided with a feeding and discharging valve, a vacuum pumping valve, a filtering layer and a filtering layer liquid discharging valve; crystallizing the concentrated material at low temperature in a vacuum rake type all-in-one dryer, then reversing the vacuum rake type all-in-one dryer to enable a filter layer to be positioned at the lowest end, and pressurizing to discharge the liquid material in the all-in-one dryer; and then heating, and carrying out vacuum drying treatment on the crystallized material under the high vacuum condition to obtain solid powder, namely the obtained product 2-methacryloyloxyethyl phosphorylcholine.

Preferably, the low-temperature crystallization temperature of the vacuum rake type all-in-one dryer is-20 ℃, and the crystallization time is 3 hours; the rake drying temperature is controlled to be 55-65 ℃, the absolute pressure is 100pa, and the processing time is 3 h.

Preferably, the purity of the refined grade 2-methacryloyloxyethyl phosphorylcholine product prepared by the method is more than or equal to 99.5%.

Compared with the prior art and technology, the invention has the beneficial effects that:

(1) the invention utilizes the multistage microchannel mixer and the microchannel reactor to carry out reactions such as substitution cyclization, esterification, amination ring opening and the like quickly, because the specific surface area of a mixing module of the microchannel reactor is large, the heating is quick and uniform, the time required by each step of reaction is greatly shortened and only needs 30 to 180 seconds, and the discharging of the microchannel reactor is laminar flow quick discharging, the product can not flow back, thereby greatly reducing the generation of by-products and improving the yield of reactants;

(2) in the preferred scheme of the invention, the raw materials are pure materials, and are synthesized in a solvent-free system, so that the post-treatment difficulty of the product is greatly reduced, the production period is shortened, the synthesized finished product is reduced, and the product quality is improved;

(3) in the preferred scheme of the invention, the discharge end of the microchannel reactor is connected with the cyclone gas-liquid separator, so that hydrogen chloride gas generated by the system can be quickly discharged, and the reaction is accelerated to proceed in the positive reaction direction;

(4) the method prepares the 2-methacryloyloxyethyl phosphorylcholine by coupling the microchannel reactor with crystallization, filtration and vacuum drying, simplifies the traditional five-step process into three-step synthesis, greatly reduces the preparation time compared with the time required by the traditional reaction kettle, shortens the preparation time from 240h to within 24h in the traditional process, improves the productivity from 0.45kg/h to 23.5kg/h, saves energy, improves the raw material conversion rate and the product yield, saves the cost, reduces the generation of byproducts, and is environment-friendly and safe.

The above description is only an outline of the technical solution of the present invention, and in order to make the technical means of the present invention more clear and to be implemented in accordance with the content of the description, several examples of different experimental effects of the present invention are described in detail below. Specific embodiments of the present invention are given in detail by the following examples.

Drawings

FIG. 1 is a schematic view of the skid-mounted equipment of the present invention;

FIG. 2 is a process flow diagram of a conventional kettle-type MPC plant.

The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this application, illustrate embodiment(s) of the invention and together with the description serve to explain the invention without limiting the invention.

Reference numbers in the figures: 11. a first material storage tank; 12. a second material storage tank; 13. a third material storage tank; 14. a fourth storage tank; 15. a fifth material storage tank; 16. a sixth storage tank; 21. a first plunger metering pump; 22. a second plunger metering pump; 23. a third plunger metering pump; 24. a fourth plunger metering pump; 25. a fifth plunger metering pump; 26. a sixth plunger metering pump; 31. a first microchannel reactor; 32. a second microchannel reactor; 33. a third microchannel reactor; 34. a delayed reaction kettle 35 and a vacuum rake type all-in-one dryer; 41. a first cyclonic gas-liquid separator; 42. a second cyclonic gas-liquid separator; 43. an exhaust fan and a tail gas treatment system; 51. a shell and tube condenser; 52. a vacuum pump set; 53. a material recovery tank; 61. a high and low temperature media interface; 62. a nitrogen interface; 71. a PLC control and power system; 81. a first mass flow meter; 82. a second mass flow meter; 83. a third mass flow meter; 84. a fourth mass flow meter; 85. a fifth mass flow meter; 86. a sixth mass flow meter; 91. frame construction and stair.

Detailed Description

The invention will be better understood from the following examples. However, those skilled in the art will readily appreciate that the description of the embodiments is only for illustrating the present invention and should not be taken as limiting the invention as detailed in the claims.

The skid-mounted equipment and the skid-mounted method for preparing 2-methacryloyloxyethyl phosphorylcholine by three-level microchannel reaction-crystallization filtration-vacuum drying coupling are realized by the skid-mounted equipment shown in the figure 1, the skid-mounted equipment comprises a skid-mounted equipment main body consisting of three-level microchannel reactors, a delay reaction kettle 34, a vacuum rake type all-in-one dryer 35, an exhaust fan and tail gas treatment system 43, a tube array condenser 51, a vacuum pump set 52 and a material recovery tank 53, and the skid-mounted equipment comprises a PLC (programmable logic controller) 71 for controlling a system; the skid-mounted equipment main body consisting of each stage of microchannel reactor comprises a material storage tank, the microchannel reactor, a plunger metering pump and a mass flow meter, wherein the material storage tank is connected with the microchannel reactor;

a feed inlet of the delay reaction kettle 34 is connected with a third-stage microchannel reactor of the skid-mounted equipment main body, a discharge outlet of the delay reaction kettle 34 is respectively connected with a tube array condenser 51 and a vacuum rake type all-in-one dryer 35, and a material recovery tank 53 is connected with the tube array condenser 51;

the vacuum pump set 52 is connected to the delay reactor 34 and the vacuum rake type all-in-one dryer 35 through the tube condenser 51, and is used for vacuuming the delay reactor 34 and the vacuum rake type all-in-one dryer 35.

The skid-mounted reaction system is arranged in a four-layer frame structure, the frame structure is provided with stairs, and a nitrogen interface 62 and a high-low temperature medium interface 61 are reserved on each layer of the frame structure.

The method for preparing 2-methacryloyloxyethyl phosphorylcholine comprises the steps of firstly, quickly synthesizing 2-chloro-2-oxo-1, 3, 2-dioxaphospholane (COP) on line through a first-stage microchannel reactor, quickly preparing 2-alkyl-2-oxo-1, 3, 2-dioxaphospholane (OPEMA) through a second-stage microchannel reactor by taking the COP as a reactant, and quickly synthesizing and preparing 2-Methacryloyloxyethyl Phosphorylcholine (MPC) through a third-stage microchannel reactor by taking OPEMA as a reactant; then, feeding the low-boiling point reactant and the solvent in the 2-methacryloyloxyethyl phosphorylcholine product into a tube-in-tube condenser in a gaseous state by a scraper film reduced pressure distillation process, carrying out heat exchange condensation to obtain a mixed solution, and collecting and recycling the mixed solution by a material recovery tank; and directly transferring the concentrated 2-methacryloyloxyethyl phosphorylcholine crude product mixed solution into a vacuum rake type all-in-one dryer for low-temperature melting crystallization purification, filtering and draining liquid, and then performing high-vacuum drying under the low-temperature condition to obtain a refined grade 2-methacryloyloxyethyl phosphorylcholine product. The method specifically comprises the following steps:

s1, introducing pure phosphorus oxychloride in the first storage tank 11 and anhydrous ethylene glycol in the second storage tank 12 into a microchannel mixer arranged in the first microchannel reactor 31 by using the first plunger metering pump 21 and the second plunger metering pump 22, mixing, then entering the first microchannel reactor 31 for rapid substitution cyclization reaction, introducing an effluent of the first microchannel reactor 31 into the first cyclone gas-liquid separator 41 for separating a gaseous product and a liquid product COP generated by the reaction, and directly transferring the generated liquid product COP into the third storage tank 13 of the second microchannel reactor; the exhaust port of the first cyclone gas-liquid separator 41 is communicated with an exhaust fan and a tail gas treatment system 43;

s2, introducing the COP in the third storage tank 13 and the anhydrous hydroxyethyl methacrylate (HEMA) in the fourth storage tank 14 into a microchannel mixer arranged in the second microchannel reactor 32 by using a third plunger metering pump 23 and a fourth plunger metering pump 24, mixing, then entering the second microchannel reactor 32 for rapid esterification, introducing the effluent of the second microchannel reactor into a second cyclone gas-liquid separator 42 for separating a gaseous product and a liquid product OPEMA generated by the reaction, and directly transferring the generated liquid product OPEMA into a fifth liquid storage tank 15 of the third microchannel reactor; the exhaust port of the second cyclone gas-liquid separator 42 is communicated with an exhaust fan and a tail gas treatment system 43;

s3, introducing the OPEMA in the fifth storage tank 15 and the trimethylamine organic solution (TMA) in the sixth storage tank 16 into a microchannel mixer arranged in a third microchannel reactor 33 by using a fifth plunger metering pump 25 and a sixth plunger metering pump 26, mixing, then introducing into the third microchannel reactor 33 for rapid amination ring opening reaction, and introducing an MPC crude product solution out of the third microchannel reactor 33 into a time-delay reaction kettle 34;

s4, carrying out reduced pressure distillation on the crude material MPC solution in the delayed reaction kettle 34 through a vacuum pump set 52, pumping the low-boiling point reactant (TMA) and the solvent in the 2-methacryloyloxyethyl phosphorylcholine product into the tubular condenser 51 in a gaseous state, carrying out heat exchange condensation to obtain a mixed solution, and collecting and recycling the mixed solution by the material recovery tank 53; and directly transferring the concentrated crude mixed solution of the 2-methacryloyloxyethyl phosphorylcholine into a vacuum rake type all-in-one dryer 35 for low-temperature melting crystallization purification, filtering and draining liquid, and then performing high-vacuum drying under the low-temperature condition to obtain a refined grade 2-methacryloyloxyethyl phosphorylcholine product.

The invention is further illustrated by the following examples, which are not intended to limit the scope of the invention.

Example 1:

as shown in fig. 1, the first plunger metering pump 21 is controlled to make pure phosphorus oxychloride at a flow rate of 60.0L/h, the second plunger metering pump 22 is controlled to make ethylene glycol simultaneously enter the microchannel mixer and the first microchannel reactor 31 at a flow rate of 34.4L/h, the reaction residence time of the first microchannel reactor is 76s, the temperature is controlled to be 25 ℃, the material is rapidly subjected to substitution cyclization reaction in the microchannel reactor, the COP mixed liquid discharged from the first microchannel reactor 31 enters the first rotational flow gas-liquid separator 41 for gas-liquid separation, and the liquid material is collected and enters the third liquid storage tank 13 of the second microchannel reactor; the exhaust port of the first cyclone gas-liquid separator 41 is communicated with an exhaust fan and a tail gas treatment system 43; when the material COP in the third storage tank 13 reaches a half liquid level, the third plunger metering pump 23 is started, feeding is carried out at a speed of 60.0L/h, the fourth plunger metering pump 24 is synchronously started, anhydrous hydroxyethyl methacrylate (HEMA) in the fourth storage tank 14 is pumped into a second-stage microchannel mixer and a second microchannel reactor 32 at a flow rate of 74.7L/h for carrying out rapid esterification, the reaction residence time of the second microchannel reactor 32 is 54s, the temperature is controlled at 65 ℃, the liquid outlet of the second microchannel reactor 32 enters a second rotational flow gas-liquid separator 42 to separate a gaseous product and a liquid product OPEMA generated by the reaction, and the generated liquid product OPEMA is directly transferred into a fifth liquid storage tank 15 of the third-stage microchannel reactor; when the material OPEMA in the fifth storage tank 15 reaches a half liquid level, the fifth plunger metering pump 25 is started, feeding is carried out at a speed of 45.0L/h, the sixth plunger metering pump 26 is synchronously started, a trimethylamine acetonitrile solution (with the concentration of 30%) in the sixth storage tank 16 is pumped into the third-stage microchannel mixer and the third microchannel reactor 33 at a flow rate of 90.0L/h for amination ring-opening reaction, the reaction residence time of the third microchannel reactor 33 is 53s, the temperature is controlled at 75 ℃, and the crude MPC product discharged from the third microchannel reactor 33 enters the delay reaction kettle 34 for continuous reaction; the reaction conditions of the time-lapse reaction kettle 34 are as follows: pressurizing with nitrogen at 0.4Mpa, controlling the temperature at 65 deg.C, and reacting for 3 h; then, the crude MPC solution in the delayed reaction kettle 34 is concentrated by the vacuum pump unit 52 under the following conditions: controlling the temperature to 65 ℃, the absolute pressure to 1000pa, and the processing time to 1 h; and then directly transferring the concentrated 2-methacryloyloxyethyl phosphorylcholine crude product mixed solution into a vacuum rake type all-in-one dryer 35 for low-temperature melting crystallization purification, wherein the low-temperature crystallization conditions are as follows: controlling the temperature to be-20 ℃ for 3 h; after filtering and discharging liquid, carrying out high vacuum drying under the low temperature condition, wherein the drying condition is as follows: controlling the temperature to 65 ℃, the absolute pressure to 100pa and the drying time to 3h to obtain the refined grade 2-methacryloyloxyethyl phosphorylcholine product. The cumulative reaction time in this example was 20 hours, the MPC purity was 99.5%, and the productivity was 23.3 kg/h.

Comparative example 1:

meanwhile, in the comparative case, a conventional synthesis process was performed using a tank reactor. Firstly, synthesizing CUP by using a 500L reaction kettle, wherein the reaction is to dropwise add ethylene glycol into a phosphorus trichloride system, the material quantity is 57L, the dropwise adding speed is 70ml/min, the reaction time and the post-treatment time in the step are 20h, and the yield in the step is 75%; secondly, slowly introducing oxygen into the obtained CUP in a 500L reaction kettle to carry out a COP synthesis reaction, wherein the aeration time is 20h, the COP post-treatment purification time is 8h, the total time is 28h, and the COP reaction material is 60%; thirdly, slowly dripping the COP solution into a mixed system of HEMA and triethylamine, wherein 5 reaction kettles are required to synchronously drip and perform parallel reaction, the dripping time is 120h, the post-treatment time of the material OPEMA is 10h, the total time is 130h, and the yield of the OPEMA is 99%; fourthly, using a conventional kettle type reactor, carrying out amination ring-opening reaction on OPEMA and trimethylamine for 24 hours, wherein the time of the ring-opening reaction is 24 hours, the time of the concentration post-treatment and crystallization drying treatment is 24 hours, the total time is 48 hours, and the yield of the reaction is 55%; the reaction time of the integrated kettle type process is 226h, and the calculated productivity is about 0.45kg/h, but the traditional process needs large volume capacity of equipment, needs to control low temperature for a long time, and has high energy consumption and low yield.

Table 1 shows the effect data of the mixing reaction performed in this example. It can be seen that the skid-mounted equipment and the skid-mounted method can greatly shorten the reaction time and improve the reaction conversion rate, and the products do not need to be subjected to aftertreatment, so that the cost is saved, and the working efficiency is improved. Compared with the conventional kettle type reaction, the microchannel reactor has higher efficiency, low energy and environmental protection, and the microchannel reactor is 53 times higher than the kettle type reactor in the aspect of capacity.

TABLE 1 reaction Effect data of examples and comparative examples

	Example 1	Comparative example 1
			Yield of the reaction	99％	55％
Capacity kg/h	23	0.45

The foregoing is merely a preferred embodiment of the invention and is not intended to limit the invention in any manner; those skilled in the art can readily practice the invention as shown and described in the drawings and detailed description herein; however, those skilled in the art should appreciate that they can readily use the disclosed conception and specific embodiments as a basis for designing or modifying other structures for carrying out the same purposes of the present invention without departing from the scope of the invention as defined by the appended claims; meanwhile, any changes, modifications, and evolutions of the equivalent changes of the above embodiments according to the actual techniques of the present invention are still within the protection scope of the technical solution of the present invention.

Claims

1. The skid-mounted equipment for preparing 2-methacryloyloxyethyl phosphorylcholine is characterized in that: the device comprises a skid-mounted equipment main body consisting of three stages of microchannel reactors, a time delay reaction kettle (34), a vacuum rake type all-in-one dryer (35), an exhaust fan and tail gas treatment system (43), a tube array condenser (51), a vacuum pump set (52) and a material recovery tank (53), and comprises a PLC (programmable logic controller) controller (71) for controlling the system; the skid-mounted equipment main body consisting of each stage of microchannel reactor comprises a material storage tank, the microchannel reactor, a plunger metering pump and a mass flow meter, wherein the material storage tank is connected with the microchannel reactor;

a feed inlet of the delay reaction kettle (34) is connected with a third-stage micro-channel reactor of the skid-mounted equipment main body, a discharge outlet of the delay reaction kettle (34) is respectively connected with a tube array condenser (51) and a vacuum rake type all-in-one dryer (35), and a material recovery tank (53) is connected with the tube array condenser (51);

the vacuum pump set (52) is communicated with the delay reaction kettle (34) and the vacuum rake type all-in-one dryer (35) through a tube still condenser (51) and is used for vacuumizing the delay reaction kettle (34) and the vacuum rake type all-in-one dryer (35).

2. The skid-mounted apparatus for preparing 2-methacryloyloxyethyl phosphorylcholine according to claim 1, wherein: the skid-mounted reaction system is arranged in a four-layer frame structure, the frame structure is provided with stairs, and each layer of the frame structure is provided with a nitrogen interface (62) and a high-low temperature medium interface (61).

3. A method for preparing 2-methacryloyloxyethyl phosphorylcholine is realized by the skid-mounted equipment of claim 1 or 2, the method is realized by firstly rapidly synthesizing 2-chloro-2-oxo-1, 3, 2-dioxaphospholane COP on line by a primary microchannel reactor, rapidly preparing 2-alkyl-2-oxo-1, 3, 2-dioxaphospholane OPEMA by taking COP as a reactant through a secondary microchannel reactor, and then rapidly synthesizing 2-methacryloyloxyethyl phosphorylcholine MPC by taking OPEMA as a reactant through a tertiary microchannel reactor; then, feeding the low-boiling point reactant and the solvent in the 2-methacryloyloxyethyl phosphorylcholine product into a tube-in-tube condenser in a gaseous state by a scraper film reduced pressure distillation process, carrying out heat exchange condensation to obtain a mixed solution, and collecting and recycling the mixed solution by a material recovery tank; and directly transferring the concentrated 2-methacryloyloxyethyl phosphorylcholine crude product mixed solution into a vacuum rake type all-in-one dryer for low-temperature melting crystallization purification, filtering and draining liquid, and then performing high-vacuum drying under the low-temperature condition to obtain a refined grade 2-methacryloyloxyethyl phosphorylcholine product.

4. The process for preparing 2-methacryloyloxyethyl phosphorylcholine according to claim 3, characterized in that: the method comprises the following steps:

introducing pure phosphorus oxychloride in a first storage tank (11) and anhydrous ethylene glycol in a second storage tank (12) into a microchannel mixer arranged in a first microchannel reactor (31) by using a first plunger metering pump (21) and a second plunger metering pump (22), mixing, then entering the first microchannel reactor (31) for rapid substitution cyclization reaction, introducing liquid discharged from the first microchannel reactor (31) into a first rotational flow gas-liquid separator (41) for separating a gaseous product and a liquid product COP generated by the reaction, and directly transferring the generated liquid product COP into a third storage tank (13) of a second microchannel reactor; the exhaust port of the first rotational flow gas-liquid separator (41) is communicated with an exhaust fan and a tail gas treatment system (43);

(II) introducing COP in the third storage tank (13) and anhydrous hydroxyethyl methacrylate HEMA in the fourth storage tank (14) into a microchannel mixer arranged in a second microchannel reactor (32) by using a third plunger metering pump 23 and a fourth plunger metering pump (24), mixing, then entering the second microchannel reactor (32) for rapid esterification, introducing an effluent of the second microchannel reactor (32) into a second cyclone gas-liquid separator (42) to separate a gaseous product and a liquid product OPEMA generated by the reaction, and directly transferring the generated liquid product OPEMA into a fifth liquid storage tank (15) of the third microchannel reactor; the exhaust port of the second rotational flow gas-liquid separator (42) is communicated with an exhaust fan and a tail gas treatment system (43);

(III) introducing the OPEMA in the fifth storage tank (15) and the trimethylamine organic solution TMA in the sixth storage tank (16) into a microchannel mixer arranged in a third microchannel reactor (33) by using a fifth plunger metering pump (25) and a sixth plunger metering pump (26), mixing, then entering the third microchannel reactor (33) for rapid amination ring-opening reaction, and entering a crude MPC solution discharged from the third microchannel reactor (33) into a time-delay reaction kettle (34);

fourthly, the vacuum pump set (52) is used for carrying out reduced pressure distillation on the material MPC crude product solution in the time delay reaction kettle (34) through a scraper film to pump the reactant TMA and the solvent with low boiling point in the 2-methacryloyloxyethyl phosphorylcholine product into a tube nest condenser (51) in a gaseous state, the reactant TMA and the solvent are converted into mixed liquid through heat exchange and condensation, and the mixed liquid is collected and recycled by a material recovery tank (53); and then directly transferring the concentrated crude mixed solution of the 2-methacryloyloxyethyl phosphorylcholine into a vacuum rake type all-in-one dryer (35) for low-temperature melting crystallization purification, filtering and draining liquid, and then performing high-vacuum drying under the low-temperature condition to obtain a refined grade 2-methacryloyloxyethyl phosphorylcholine product.

5. The process for preparing 2-methacryloyloxyethyl phosphorylcholine according to claim 4, characterized in that: the volume of the time-delay reaction kettle (34) is 200L, and the time-delay reaction kettle is provided with a double-layer jacket reaction kettle which is provided with a high-speed stirring motor and a stirring paddle, wherein the stirring paddle in the kettle is of a scraper type, and the scraper is made of polytetrafluoroethylene and is 20mm away from the inner wall of the reaction kettle; the delay reaction kettle is provided with a weighing module and a liquid level meter, the mass and the volume of materials in the storage tank can be accurately measured, the storage tank is provided with a feed valve, a discharge valve, a vacuum pumping valve, a nitrogen interface and a vacuum pressure gauge, and the discharge valve at the bottom of the storage tank is a temperature measurement discharge valve; the heat exchange area of the shell and tube condenser (51) is 1 square meter, and the temperature is controlled to be-40 ℃; the vacuum pump set (52) is a three-stage Roots vacuum pump set, the ultimate vacuum is 0.01pa, the air suction amount is 200L/s, and an air outlet of the vacuum pump set (52) is connected with an exhaust fan-tail gas treatment system (43); the vacuum rake type all-in-one dryer (35) is of a spherical structure, has an effective volume of 150L and is provided with a jacket temperature control layer communicated with the high-low temperature medium interface (61); the vacuum rake type all-in-one dryer (35) is provided with a feeding and discharging valve, a vacuum pumping valve, a filtering layer and a filtering layer liquid discharging valve; crystallizing the concentrated material at low temperature in a vacuum rake type all-in-one dryer, then reversing the vacuum rake type all-in-one dryer to enable a filter layer to be positioned at the lowest end, and pressurizing to discharge the liquid material in the all-in-one dryer; and then heating, and carrying out vacuum drying treatment on the crystallized material under the high vacuum condition to obtain solid powder, namely the obtained product 2-methacryloyloxyethyl phosphorylcholine.

6. The process for preparing 2-methacryloyloxyethyl phosphorylcholine according to claim 4, characterized in that: the molar ratio of the phosphorus oxychloride to the ethylene glycol in the step (one) is 1.05: 1; the temperature of the first micro-channel reactor (31) and the micro-channel mixer is controlled to be 0-25 ℃; the flow rate of the first plunger metering pump (21) is 0-60.0L/h, and the flow rate of the second plunger metering pump (22) is 0-34.4L/h.

7. The process for preparing 2-methacryloyloxyethyl phosphorylcholine according to claim 4, characterized in that: the temperature of the second microchannel reactor (32) and the microchannel mixer in the step (II) is controlled to be 45-65 ℃; the flow rate of the third plunger metering pump 23 is 0-60.0L/h, and the flow rate of the fourth plunger metering pump (24) is 0-74.7L/h.

8. The process for preparing 2-methacryloyloxyethyl phosphorylcholine according to claim 4, characterized in that: controlling the temperature of the third microchannel reactor (33) and the microchannel mixer in the step (III) to be 60-75 ℃; the flow rate of the fifth plunger metering pump (25) is 0-45.0L/h, and the flow rate of the sixth plunger metering pump (26) is 0-90.0L/h;

the trimethylamine organic solution TMA is a trimethylamine acetonitrile solution and a trimethylamine tetrahydrofuran solution, wherein the trimethylamine accounts for 30% by mass; the reaction conditions of the time-delay reaction kettle (34) are as follows: controlling the temperature to 65 ℃, pressurizing the nitrogen by 0.4Mpa, stirring at the speed of 400rpm, and reacting for 3 h; the concentration condition of the delayed reaction kettle is that the temperature is controlled to be 65 ℃, the absolute pressure is 1000pa, and the processing time is 1 h.

9. The process for preparing 2-methacryloyloxyethyl phosphorylcholine according to claim 4, characterized in that: the low-temperature crystallization temperature of the vacuum rake type all-in-one dryer (35) in the step (four) is-20 ℃, and the crystallization time is 3 hours; the rake drying temperature is controlled to be 55-65 ℃, the absolute pressure is 100pa, and the processing time is 3 h.

10. The process for preparing 2-methacryloyloxyethyl phosphorylcholine according to claim 4, characterized in that: the liquid holdup of a micro-channel mixer of the three-stage micro-channel reactor is 100mL, and the characteristic dimension of a channel is 200 micrometers; the microchannel reactor is made of Hastelloy, has the characteristic dimension of 200 micrometers, the liquid holdup of 2000mL and the heat exchange capacity per unit volume of 33MW per square meter K, is provided with an online temperature and pressure detection system, and is respectively provided with a temperature control interface and a high-low temperature medium interface (61) for quick assembly connection.