A reaction device for the production of cefuroxime sodium

Abstract

The present application relates to the technical field of cefuroxime sodium production, and provides a reaction device for cefuroxime sodium production, which comprises a standby liquid preparation kettle and a cefuroxime sodium preparation kettle, the cefuroxime sodium preparation kettle comprises a reaction kettle one and a reaction kettle two, the shell of the reaction kettle one and the reaction kettle two sequentially comprises a reaction shell, a temperature control shell and a heat preservation shell from inside to outside, a temperature control spiral pipe is arranged in the temperature control cavity between the inner wall of the temperature control shell and the outer wall of the reaction shell, the temperature control spiral pipe forms a loop with an external temperature control medium supply end, and an auxiliary electric heating wire is arranged in the temperature control shell. The present application integrates multiple steps of reactions in one device, improves production efficiency, reduces the risk of intermediate product pollution and degradation, and provides a stable thermal environment background for the interior through a unique three-layer shell temperature control structure design, solves the disadvantages of traditional jacket temperature control hysteresis and unevenness, and improves the operability and maintainability of the equipment through an auxiliary jacking assembly.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of cefuroxime sodium production, and particularly relates to a reaction device for cefuroxime sodium production. BACKGROUND

[0002] As an important second-generation cephalosporin antibiotic, cefuroxime sodium is usually produced through multiple reactions such as hydrolysis, amidation, carbamoylation and salt formation. At present, the industrial production mostly adopts a batch kettle reaction, which has the following significant technical problems: (1) The batch kettle reaction is a discrete equipment layout, and each reaction unit (such as a hydrolysis kettle, an amidation kettle, a carbamoylation kettle, a crystallization kettle, etc.) is independent of each other. This layout causes the production process to be seriously fragmented, lengthy and tedious. The intermediate product must be frequently transferred and transported between steps, which not only greatly reduces the production efficiency, increases the production cycle and energy consumption, but also significantly increases the risk of exposure of the material to the external environment during each transfer process, which easily introduces impurities, absorbs moisture or degrades, especially for cephalosporins which are sensitive to water, oxygen and temperature, thereby resulting in a decrease in the yield and purity of the final product and quality fluctuations.

[0003] (2) The synthesis of cefuroxime sodium has extremely stringent requirements for the reaction temperature. The heat exchange efficiency of the reaction kettle in the prior art is low, and the heat preservation design is often insufficient, and the heat insulation performance is poor (on the one hand, when maintaining a low-temperature reaction, the heat from the external environment continuously invades, so that the refrigeration system needs to continuously operate at high load to compensate, causing huge energy waste; on the other hand, when drying is required, heat is also lost in large amounts, affecting the stability and sustainability of the temperature control effect, and the fluctuation of the external environment temperature will directly interfere with the heat balance inside the reaction kettle). The temperature control has serious hysteresis, unevenness and instability.

[0004] (3) The traditional reaction equipment, especially the large kettle used for the crystallization and drying of the final product, is mostly a fixed integrated structure. This structure makes it extremely inconvenient to take out the final product, which usually needs to be manually taken out through the top manhole. When the equipment interior needs to be thoroughly cleaned, maintained or fault repaired, the space is extremely limited, the operation is difficult, the repair personnel often need to enter the equipment interior, which has safety hazards, and causes the equipment to be shut down for a long time, seriously affecting the continuity of production and the use efficiency of the equipment. SUMMARY

[0005] The application provides a reaction device for cefuroxime sodium production to solve at least one of the technical problems mentioned above. The application is implemented through the following technical scheme:

[0006] The utility model provides a reaction device for cefuroxime sodium production, including standby liquid preparation kettle and cefuroxime sodium preparation kettle, cefuroxime sodium preparation kettle is connected in the output of standby liquid preparation kettle, and standby liquid preparation kettle is used to prepare furanoyl chloride side chain's acetone solution;

[0007] Cefuroxime sodium preparation kettle includes reaction kettle one and reaction kettle two, and reaction kettle two is connected with reaction kettle one through auxiliary jacking assembly, and auxiliary jacking assembly is used to drive reaction kettle one to move up and down relative to reaction kettle two, reaction kettle one is used to hydrolyze 7-ACA as starting reactant to obtain 7-DACA, and obtains DCCF solid powder through the reaction with furanoyl chloride side chain's acetone solution, and DCCF solid powder is exported to reaction kettle two, and reaction kettle two is used to carry out the carbamoylation modification of 3-position hydroxymethyl to DCCF to obtain cefuroxime acid, and carries out sodium conversion operation to obtain cefuroxime sodium;

[0008] The shell of reaction kettle one and reaction kettle two includes reaction shell, temperature control shell and heat preservation shell from inside to outside in turn, and the temperature control cavity between the inner wall of temperature control shell and the outer wall of reaction shell is arranged with temperature control spiral pipe, and the temperature control spiral pipe forms a loop with the outside temperature control medium supply end, and the auxiliary electric heating wire is integrated in the temperature control shell.

[0009] Preferably, the standby liquid preparation kettle is rotatably connected with an electric stirring paddle, and a feeding cover is rotatably connected at a feeding port of the standby liquid preparation kettle, the feeding port is used for feeding furan ammonium salt, the standby liquid preparation kettle is connected with a liquid delivery pipe one, a liquid delivery pipe two and a liquid delivery pipe three, the liquid delivery pipe one is communicated with a benzene liquid supply end for delivering benzene to the standby liquid preparation kettle, the liquid delivery pipe two is communicated with an oxalyl chloride and benzene mixed solution liquid supply end for delivering the oxalyl chloride and benzene mixed solution to the standby liquid preparation kettle, and the liquid delivery pipe three is communicated with an acetone liquid supply end for delivering acetone to the standby liquid preparation kettle, the standby liquid preparation kettle is fixedly connected with a catalyst communication port, the catalyst communication port is communicated with a dimethylacetamide liquid supply end, and the standby liquid preparation kettle is provided with a furanoyl chloride side chain flow guide pipe at the bottom, the furanoyl chloride side chain flow guide pipe is communicated with the top of the reaction kettle one.

[0010] Preferably, the auxiliary jacking assembly includes two symmetrically arranged jacking hydraulic cylinders and a top ring, the two jacking hydraulic cylinders are bolted to the outer wall of the reaction kettle two, the output ends of the two jacking hydraulic cylinders are fixedly connected to the bottom of the top ring, and the reaction kettle one is fixedly connected with an annular kettle waist, the top of the top ring is used to abut against the bottom surface of the annular kettle waist, so that the reaction kettle one is jacked up under the action of the jacking hydraulic cylinders.

[0011] The standby liquid preparation kettle is installed on a hydraulic lifting frame, and the hydraulic lifting frame and the jacking hydraulic cylinders are electrically connected with a cefuroxime sodium production control system, and the cefuroxime sodium production control system can control the synchronous extension and contraction of the hydraulic lifting frame and the jacking hydraulic cylinders.

[0012] Preferably, the top of the reactor is provided with a plurality of DCCF reactant feeding pipes and a pressure detector, the DCCF reactant feeding pipes are used for feeding the reactants in the preparation of DCCF solid powder, and the pressure detector is used for detecting the pressure in the reactor; the side wall of the reactor is provided with a mounting groove, and a mounting window is hingedly connected to the mounting groove; the mounting groove is used for mounting a camera; the bottom of the reactor is provided with a DCCF solid powder output pipe; and the inside of the reactor is provided with a DCCF solid powder preparation assembly, which is used for stirring, filtering and collecting the solid powder in the preparation of DCCF solid powder.

[0013] The side wall of the reaction shell of the reactor is in communication with an external vacuum pump; the bottom of the reaction shell of the reactor is provided with a plurality of electromagnetic liquid discharge channels; and the temperature control shell and the heat preservation shell of the reactor form a liquid discharge cavity, and the bottom of the liquid discharge cavity is provided with two groups of liquid discharge connecting holes, which are in communication with an external waste liquid collection bin.

[0014] Preferably, the DCCF solid powder preparation assembly comprises a rotating shaft driven by a rotating shaft driving assembly on the reactor, a meshing cylinder fixedly connected to the rotating shaft, a discharging circular table fixedly connected to the bottom of the meshing cylinder, the discharging circular table being large at the top and small at the bottom, a stirring and filtering basket slidably connected to the meshing cylinder, the stirring and filtering basket comprising a meshing part and a basket body fixedly connected to the meshing part, a meshing groove formed in the meshing cylinder, a meshing block fixedly connected to the inner wall of the meshing part, the meshing block being slidably connected to the meshing groove, a basket body lifting driving assembly provided on the inner wall of the reaction shell of the reactor, and the working end of the basket body lifting driving assembly being slidably connected to the annular sliding groove of the basket body, the basket body lifting driving assembly being used for driving the basket body to move up and down.

[0015] The inner wall of the reaction shell of the reactor is hingedly connected to an electric collecting scraper, which is used for scraping off the DCCF solid powder attached to the basket body.

[0016] Preferably, the basket body lifting driving assembly comprises two groups of symmetrically arranged electric lead screws, the electric lead screws being rotatably connected to the lead screw mounting cavities in the reaction shell of the reactor, a lifting nut being threadedly connected to the electric lead screws, a micro guide block and a T-shaped connecting block being fixedly connected to the lifting nut, the micro guide block being slidably connected to the lead screw mounting cavities away from the lifting nut, and the T-shaped connecting block being slidably connected to the annular sliding groove away from the lifting nut.

[0017] Preferably, the second reaction kettle comprises a plurality of cefuroxime sodium reactant feeding pipes for feeding reactants in the preparation of cefuroxime sodium, and a second pressure detector for detecting the pressure in the second reaction kettle. The reaction shell of the second reaction kettle is connected with an ice water supply cylinder. The bottom of the reaction shell of the second reaction kettle is provided with a plurality of electromagnetic liquid discharge channels two. The temperature control shell of the second reaction kettle and the heat preservation shell of the second reaction kettle form a liquid discharge cavity two. The bottom of the heat preservation shell of the second reaction kettle is provided with a waste pipe, the end of the waste pipe away from the heat preservation shell of the second reaction kettle is connected with an external waste liquid collection bin two, and the side wall of the reaction shell of the second reaction kettle is communicated with an external vacuum pump.

[0018] The second reaction kettle is rotatably connected with a rotating shaft two, which is driven by a rotating shaft two driving assembly. The rotating shaft two is fixedly connected with a liquid discharge cavity scraping strip, which is rotatably connected in the liquid discharge cavity two. The rotating shaft two is fixedly connected with two symmetrical meshing guide strips. The rotating shaft two is slidably connected with a cefuroxime sodium filter screen assembly. The cefuroxime sodium filter screen assembly comprises a cefuroxime sodium filter screen and a meshing sliding sleeve. The inner wall of the meshing sliding sleeve is slidably connected with the meshing guide strips on the rotating shaft two. The cefuroxime sodium filter screen is fixedly connected with the meshing sliding sleeve. The cefuroxime sodium filter screen is fixedly connected with an auxiliary stirring paddle.

[0019] The second reaction kettle further comprises a DCCF acetonitrile reaction liquid preparation cylinder, which is rotatably connected with the DCCF solid powder output pipe of the first reaction kettle. The DCCF acetonitrile reaction liquid preparation cylinder is used for preparing DCCF acetonitrile reaction liquid.

[0020] Preferably, the DCCF acetonitrile reaction liquid preparation cylinder comprises a preparation cylinder body, which is rotatably connected with the DCCF solid powder output pipe of the first reaction kettle. The DCCF solid powder output pipe is communicated with an external acetonitrile supply end through an acetonitrile supply port. A cylinder body meshing groove is formed in the bottom of the preparation cylinder body, which is used for cooperating with the rotating shaft two and the meshing guide strips.

[0021] The bottom of the preparation cylinder body is provided with a plurality of electromagnetic liquid discharge channels three. The inner wall of the preparation cylinder body is fixedly connected with a fixed stirring paddle.

[0022] Preferably, a reaction device for the production of cefuroxime sodium further comprises:

[0023] A component monitoring module comprises a spectrum probe arranged inside the first reaction kettle and the second reaction kettle. The spectrum probe is used for real-time acquisition of the original spectrum signal of the material in the corresponding reaction kettle.

[0024] A data analysis module is used for receiving the original spectrum signal of the material in the first reaction kettle and the second reaction kettle, and inputting it into a trained concentration determination model to obtain the concentration data of at least one key component in the reaction system corresponding to the first reaction kettle and the second reaction kettle.

[0025] The feedback execution module is configured to compare the concentration data of at least one key component in the reaction systems corresponding to the first reaction kettle and the second reaction kettle with preset process standard values, and generate control instructions to dynamically adjust the execution components of the first reaction kettle and the second reaction kettle, so that the reaction process conforms to the preset process trajectory.

[0026] Preferably, the basket is provided with at least one ultrasonic transducer array.

[0027] Compared with the prior art, the present application has the following beneficial effects:

[0028] (1) The present application integrates multiple reaction steps in one device, greatly simplifying the production process, reducing material transfer steps, improving production efficiency, and reducing the risk of intermediate product pollution and degradation;

[0029] (2) The unique three-layer shell temperature control structure design of the first reaction kettle and the second reaction kettle greatly reduces the influence of external environmental temperature fluctuations on the reaction system, providing a stable thermal environment for the interior, laying the foundation for energy saving and sustainable temperature control; the circulating loop formed by the temperature control spiral pipe and the external temperature control medium supply end can quickly switch between low-temperature medium and high-temperature medium according to instructions, and through the spiral pipe structure, it can realize large-area and efficient heat exchange with the reaction shell wall, thereby quickly and uniformly removing or supplying heat, solving the problems of traditional jacket temperature control hysteresis and unevenness; the auxiliary heating wire integrated in the temperature control shell can work independently or cooperatively with the high-temperature medium as a distributed heat source, and is used for precise compensation heating to ensure temperature stability and product yield and quality;

[0030] (3) The auxiliary jacking assembly is provided to enable the first reaction kettle to be jacked up, thereby forming a material taking port between the first reaction kettle and the second reaction kettle, which greatly facilitates the removal of the final product in the second reaction kettle and the maintenance and cleaning of the entire system, improving the operability and maintainability of the equipment;

[0031] (4) The present application creatively integrates the functions of stirring, filtering and crystal collection in a single stirring and filtering basket component, which can complete the reaction stirring, crystal growth, filtering, washing, vacuum drying and solid product unloading processes through the combination of lifting and rotating movements, and has the advantages of compact structure, high function integration, significantly simplified equipment structure and reduced manufacturing cost; the electric collection scraping strip can effectively scrape off the dry solid powder adhering to the inner wall of the basket, solving the industry problem of solid material sticking to the wall and incomplete unloading in the filtering and drying integrated equipment, and ensuring the complete recovery of the product and the self-cleaning ability of the equipment;

[0032] (5) The present invention adopts the transmission method of electric screw and lifting nut, which has high transmission accuracy and accurate positioning, and can achieve precise control of the position of the stirring filter basket; the sliding connection design of T-shaped connecting block and annular groove cleverly decouples the lifting drive from the rotational motion of the basket, so that the basket can rotate freely without interfering with the lifting motion, realizing the normal operation of the stirring function. The structure is ingenious and the operation is reliable. Attached Figure Description

[0033] The accompanying drawings are provided to further illustrate the invention and form part of the specification. They are used in conjunction with embodiments of the invention to explain the invention and do not constitute a limitation thereof. In the drawings:

[0034] Figure 1 This is a three-dimensional schematic diagram of a reaction apparatus for the production of cefuroxime sodium provided by the present invention;

[0035] Figure 2 This is a schematic diagram of the standby liquid preparation vessel in this invention;

[0036] Figure 3 This is a schematic diagram of the structure of the cefuroxime sodium preparation vessel in this invention;

[0037] Figure 4 This is a cross-sectional view of the cefuroxime sodium preparation vessel in this invention;

[0038] Figure 5 For the present invention Figure 4 A magnified view of a section at point A in the middle;

[0039] Figure 6 This is a cross-sectional view of reactor one in this invention;

[0040] Figure 7 For the present invention Figure 6 A magnified view of a section at point B in the middle;

[0041] Figure 8 This is a cross-sectional view of reactor 2 in this invention;

[0042] Figure 9 This is a schematic diagram of the installation of the meshing sleeve in this invention;

[0043] Figure 10 For the present invention Figure 4 A magnified view of a section at point C;

[0044] Figure 11 This is a schematic diagram of the installation at the bottom of the DCCF acetonitrile reaction solution preparation cylinder in this invention;

[0045] Figure 12 This is a production route diagram for cefuroxime sodium in this invention.

[0046] In the figure: 1, standby liquid preparation kettle; 10, feeding cover; 11, liquid delivery pipe one; 12, liquid delivery pipe two; 13, liquid delivery pipe three; 14, catalyst communication port; 15, furanoyl chloride side chain guide pipe; 2, cefuroxime sodium preparation kettle; 20, reaction kettle one; 200, rotating shaft one; 2000, rotating shaft one driving motor; 2001, speed reducer; 2002, meshing cylinder; 2003, discharging circular table; 2004, meshing groove; 2005, stirring filter basket; 2006, meshing part; 2007, basket body; 2008, meshing block; 2009, annular sliding slot; 201, DCCF reactant feeding pipe; 2010, electric lead screw; 2011, lead screw mounting cavity; 2012, lifting nut; 2013, micro guide block; 2014, T-shaped connecting block; 2015, electric collection scraping strip; 202, pressure detection meter one; 203, mounting groove; 204, mounting window; 205, DCCF solid powder output pipe; 206, electromagnetic liquid discharge passage one; 2060, liquid discharge cavity one; 2061, liquid discharge connecting hole; 21, reaction kettle two; 210, cefuroxime sodium reactant feeding pipe; 211, ice water supply cylinder; 212, electromagnetic liquid discharge passage two; 2120, waste discharge pipe; 213, liquid discharge cavity two; 214, rotating shaft two; 2140, rotating shaft two driving motor; 2141, bevel gear one; 2142, bevel gear two; 215, liquid discharge cavity scraping strip; 216, meshing guide strip; 217, cefuroxime sodium filter screen; 218, meshing sliding sleeve; 219, auxiliary stirring paddle; 22, DCCF acetonitrile reaction liquid preparation cylinder; 220, preparation cylinder body; 221, cylinder body meshing groove; 222, electromagnetic liquid discharge passage three; 223, fixed stirring paddle; 224, acetonitrile supply port; 3, reaction shell; 30, temperature control shell; 31, heat preservation shell; 32, temperature control cavity; 33, temperature control spiral pipe; 34, annular kettle waist; 4, hydraulic lifting frame; 40, lifting hydraulic cylinder; 41, lifting ring. DETAILED DESCRIPTION

[0047] The preferred embodiments of the present application are described below in conjunction with the accompanying drawings, in which it is understood that the preferred embodiments described herein are merely intended to illustrate and explain the present application, and are not intended to limit the present application.

[0048] In addition, the descriptions such as "first", "second" and the like in the present application are only for the purpose of description, and are not intended to particularly indicate the order or sequence, nor to limit the present application, but only to distinguish the components or operations described by the same technical terms, and cannot be understood as indicating or implying the relative importance of the indicated technical features or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first", "second" can explicitly or implicitly include at least one of the features. In addition, the technical solutions and technical features of various embodiments can be combined with each other, but it must be based on the realization of the person skilled in the art, and when the combination of technical solutions appears to be contradictory or unachievable, it should be considered that the combination of technical solutions does not exist and is not within the protection scope required by the present application.

[0049] Embodiment 1: The embodiment of the present application provides a reaction device for the production of cefuroxime sodium, as shown in the figure, comprising a standby liquid preparation kettle 1 and a cefuroxime sodium preparation kettle 2, the cefuroxime sodium preparation kettle 2 is connected to the output end of the standby liquid preparation kettle 1, and the standby liquid preparation kettle 1 is used to prepare an acetone solution of furanoyl chloride side chain; Figures 1-12

[0050] The cefuroxime sodium preparation kettle 2 comprises a reaction kettle one 20 and a reaction kettle two 21, the reaction kettle two 21 and the reaction kettle one 20 are connected through an auxiliary jacking assembly, the auxiliary jacking assembly is used to drive the reaction kettle one 20 to move up and down relative to the reaction kettle two 21, the reaction kettle one 20 is used to take 7-ACA as a starting reactant, hydrolyze to obtain 7-DACA, and react with the acetone solution of furanoyl chloride side chain to obtain DCCF solid powder, and output the DCCF solid powder to the reaction kettle two 21, the reaction kettle two 21 is used for acylating modification of 3-hydroxymethyl of DCCF to obtain cefuroxime acid, and performing sodium conversion operation to obtain cefuroxime sodium;

[0051] The shell of the reaction kettle one 20 and the reaction kettle two 21 comprises, from inside to outside, a reaction shell 3, a temperature control shell 30 and a heat preservation shell 31 in sequence, a temperature control spiral pipe 33 is arranged in a temperature control cavity 32 between the inner wall of the temperature control shell 30 and the outer wall of the reaction shell 3, the temperature control spiral pipe 33 forms a loop with an external temperature control medium supply end, and an auxiliary electric heating wire is integrated in the temperature control shell 30.

[0052] In this embodiment, the reaction kettle one 20 is provided with a sealing strip at the bottom, which is used to ensure the sealing between the bottom of the reaction kettle one 20 and the top of the reaction kettle two 21.

[0053] In this embodiment, the reaction kettle one 20 and the reaction kettle two 21 are both provided with electromagnetic exhaust holes, and the cefuroxime sodium production control system can control the on-off of the electromagnetic exhaust holes based on the pressure detection results in the reaction kettle one 20 and the reaction kettle two 21 and the reaction requirements.

[0054] ​In this embodiment, the temperature control spiral pipe 33, the external temperature control medium supply end and the auxiliary electric heating wire together constitute a high-precision two-way temperature control system for realizing accurate control of the temperature of the material inside the reaction shell 3. The external temperature control medium supply end at least includes a low-temperature medium storage tank, a high-temperature medium storage tank, a circulating pump, and a three-way valve or a series of electromagnetic valves for switching the flow direction of the medium. The external temperature control medium supply end is connected with the inlet and outlet of the temperature control spiral pipe 33 through pipelines to form a closed circulation loop. The control process is as follows:

[0055] Refrigeration or cooling mode: when it is necessary to reduce and maintain the reaction material to a low temperature, such as 0-5°C for hydrolysis reaction or 0°C for amidation reaction, the cefuroxime sodium production control system issues an instruction to control the switching valve in the external temperature control medium supply end to open the low-temperature medium passage. The circulating pump drives the low-temperature medium to flow through the temperature control spiral pipe 33. Since the temperature control cavity 32 tightly wraps the reaction shell 3, the low-temperature medium exchanges heat with the wall of the reaction shell 3 through the pipe wall of the temperature control spiral pipe 33, thereby continuously and uniformly removing the reaction heat, rapidly reducing the temperature of the material and stabilizing it at the set value. Through real-time monitoring feedback by the temperature sensor inside the reaction shell 3, the cefuroxime sodium production control system algorithm dynamically adjusts the flow and temperature of the low-temperature medium to realize accurate temperature control within ±0.5°C.

[0056] Heating or heat preservation mode: when it is necessary to heat or heat preservation, such as 40°C for vacuum drying process, the cefuroxime sodium production control system first determines the required temperature. If the required temperature is moderate, such as 40°C for drying, the switching valve opens the high-temperature medium passage, and the circulating pump drives the high-temperature medium to flow through the temperature control spiral pipe 33 to provide heat to the reaction system to 40°C. If the required temperature is higher and the reaction itself has no intense heat release, the auxiliary electric heating wire embedded in the temperature control shell 30 is preferentially or simultaneously started to heat. The auxiliary electric heating wire as a distributed heat source can uniformly radiate heat to the temperature control cavity 32, and then conduct heat to the material through the wall of the reaction shell 3. In this mode, the cefuroxime sodium production control system also dynamically adjusts the heating power of the auxiliary electric heating wire and / or the flow of the high-temperature medium according to the feedback of the temperature sensor through the algorithm to ensure that the temperature is stable within the set range.

[0057] The working principle and beneficial effects of the above technical solution are as follows: during work, the standby liquid preparation kettle 1 first prepares the acetone solution of the furanoyl chloride side chain in standby, the reaction kettle one 20 is used to perform the hydrolysis reaction of 7-ACA as the starting material to prepare 7-DACA aqueous solution, and then the acetone solution of the furanoyl chloride side chain from the standby liquid preparation kettle 1 is subjected to amidation reaction to generate DCCF, and after crystallization, crystal growth, filtration, washing and vacuum drying, DCCF solid powder is obtained, and then the reaction kettle two 21 receives the DCCF solid powder output by the reaction kettle one 20, and sequentially performs chlorosulfonylation, hydrolysis, extraction, decolorization, salt formation and crystallization, washing and vacuum drying, and finally the cefuroxime sodium finished product is obtained.

[0058] Among them, the auxiliary jacking assembly can realize the lifting movement of the reaction kettle one 20 relative to the reaction kettle two 21, which is convenient for maintenance and material taking, and the three-layer shell structure of the reaction kettle one 20 and the reaction kettle two 21 and the built-in temperature control spiral pipe 33 and auxiliary heating wire can accurately realize the heat supply and removal of the high and low temperature environment and the vacuum drying environment required for the reaction, and ensure that each step of the reaction is carried out under the best temperature conditions.

[0059] The present application integrates the core steps of cefuroxime sodium production in the standby liquid preparation kettle 1, the reaction kettle one 20 and the reaction kettle two 21, and realizes the efficient and portable output of the cefuroxime sodium finished product.

[0060] All material inlet and outlet pipelines, flow guide pipes and liquid discharge channels on the standby liquid preparation kettle 1, the reaction kettle one 20, the reaction kettle two 21 and the DCCF acetonitrile reaction liquid preparation cylinder 22 are provided with on-off control valves such as electromagnetic valves, pneumatic valves or electric valves, all of which are connected with the cefuroxime sodium production control system signal, and are controlled by the cefuroxime sodium production control system according to the preset program to realize accurate and automatic control of the material flow path of each reaction section, ensure effective isolation between different reaction stages, avoid material mixing and cross contamination, and is the core basis for realizing the whole process automation and closed production.

[0061] The present application greatly simplifies the production process, reduces the material transfer link, improves the production efficiency, and reduces the risk of intermediate product pollution and degradation by integrating multiple reactions in a set of devices. The unique three-layer shell temperature control structure design of the reaction kettle one 20 and the reaction kettle two 21, the excellent heat insulation performance of the heat preservation shell 31 greatly isolates the influence of the external environment temperature fluctuation on the reaction system, provides a stable thermal environment background for the inside, and lays the foundation for energy saving and sustainable temperature control; the circulating loop formed by the temperature control spiral pipe 33 and the external temperature control medium supply end can quickly switch low temperature medium or high temperature medium according to the instruction, realize large area and efficient heat exchange with the reaction shell 3 wall through the spiral pipe structure, and quickly and uniformly remove or supply heat, solving the problems of traditional jacket temperature control hysteresis and unevenness; the auxiliary heating wire integrated in the temperature control shell 30 can work cooperatively or independently with the high temperature medium as a distributed heat source with fast response, and is used for accurate compensation heating to ensure temperature stability and guarantee high yield and high quality of the product; by setting the auxiliary jacking assembly, the reaction kettle one 20 can be jacked up to form a material taking port between the reaction kettle one 20 and the reaction kettle two 21, which greatly facilitates the taking out of the final product in the reaction kettle two 21 and the maintenance and cleaning of the whole system inside, and improves the operability and maintainability of the equipment.

[0062] In example 2, on the basis of example 1, the standby liquid preparation kettle 1 is rotatably connected with an electric stirring paddle, and the standby liquid preparation kettle 1 is rotatably connected with a feeding cover 10 at the feeding port for feeding furan ammonium salt. The standby liquid preparation kettle 1 is connected with a liquid delivery pipe one 11, a liquid delivery pipe two 12 and a liquid delivery pipe three 13. The liquid delivery pipe one 11 is connected with a benzene liquid supply end for delivering benzene to the standby liquid preparation kettle 1. The liquid delivery pipe two 12 is connected with an oxalyl chloride and benzene mixed solution liquid supply end for delivering the oxalyl chloride and benzene mixed solution to the standby liquid preparation kettle 1. The liquid delivery pipe three 13 is connected with an acetone liquid supply end for delivering acetone to the standby liquid preparation kettle 1. The standby liquid preparation kettle 1 is fixedly connected with a catalyst communication port 14 which is connected with a dimethylacetamide liquid supply end. The bottom of the standby liquid preparation kettle 1 is provided with a furan acyl chloride side chain flow guide pipe 15 which is connected with the top of the reaction kettle one 20.

[0063] The working principle and beneficial effects of the above technical solution are as follows:

[0064] The preparation process of the acetone solution of furanoyl chloride side chain includes: opening the feeding cover 10, feeding a preset amount of furan ammonium salt into the standby liquid preparation kettle 1 through the feeding port by the feeding auger, then closing the feeding cover 10, at the same time, feeding benzene into the standby liquid preparation kettle 1 through the liquid conveying pipe one 11, starting the electric stirring paddle to mix and stir the furan ammonium salt and benzene, at the same time, adding dimethylacetamide into the standby liquid preparation kettle 1 through the catalyst communication port 14 to catalyze, after stirring for a preset time, feeding the oxalyl chloride and benzene mixed solution into the standby liquid preparation kettle 1 through the liquid conveying pipe two 12, stirring again until a light yellow solution with a small amount of white solid suspension is obtained, and the white solid suspension is automatically filtered and fished; optionally, a fishing net is arranged in the standby liquid preparation kettle 1, and the fishing net plays a filtering role to fish the white solid suspension into the fishing net during the stirring process; then the light yellow solution is heated by the heating component inside the standby liquid preparation kettle 1, so that the furanoyl chloride side chain crystals are precipitated, then the acetone is conveyed into the standby liquid preparation kettle 1 through the liquid conveying pipe three 13, and finally the acetone solution of the furanoyl chloride side chain, that is, the acetone solution of SMIF-CL, is formed, and is ready for standby.

[0065] The present application realizes the directional, closed and quantitative feeding of furan ammonium salt, benzene or alternative solvents such as toluene, oxalyl chloride benzene solution, acetone and catalyst dimethylacetamide, avoids the errors and dangers that may be caused by manual feeding, improves the automation degree and safety of the standby process, and the design of the furanoyl chloride side chain guide pipe 15 enables the prepared acetone solution of the furanoyl chloride side chain to be directly conveyed to the reaction kettle one 20 through a closed pipeline to participate in the subsequent amidation reaction, realizes the seamless and closed transfer of the materials, guarantees the stability of the intermediates which have strict requirements for anhydrous environment, improves the production efficiency, and reduces the leakage risk of volatile organic solvents.

[0066] In the embodiment 3, on the basis of the embodiment 1, the auxiliary jacking assembly includes two symmetrically arranged jacking hydraulic cylinders 40 and a top ring 41, the two jacking hydraulic cylinders 40 are both bolted to the outer wall of the reaction kettle two 21, the output ends of the two jacking hydraulic cylinders 40 are both fixedly connected to the bottom of the top ring 41, the reaction kettle one 20 is fixedly connected with a ring-shaped kettle waist 34, and the top of the top ring 41 is used to abut against the bottom surface of the ring-shaped kettle waist 34, so as to be jacked upward by the jacking hydraulic cylinders 40.

[0067] The standby liquid preparation kettle 1 is installed on the hydraulic lifting frame 4, and the hydraulic lifting frame 4 and the jacking hydraulic cylinders 40 are both electrically connected with the cefuroxime sodium production control system, and the cefuroxime sodium production control system can control the synchronous extension and retraction of the hydraulic lifting frame 4 and the jacking hydraulic cylinders 40.

[0068] In the embodiment, the top ring 41 is composed of two bolt-connected half top rings, and the top ring 41 is matched with the outer wall of the reactor 20.

[0069] The working principle and beneficial effects of the technical solution are as follows: after the production of cefuroxime sodium is completed, the hydraulic lifting frame 4 and the jacking hydraulic cylinder 40 are controlled by the cefuroxime sodium production control system to be synchronously elongated, at this time, the top ring 41 is subjected to upward thrust under the joint action of the jacking hydraulic cylinder 40 and the top ring 41, so that the reactor 20 is jacked upward, a material taking opening is formed between the reactor 20 and the reactor 21, and the staff can conveniently take out the cefuroxime sodium product in the reactor 21, and meanwhile, the design of the auxiliary jacking assembly also facilitates the maintenance and inspection of the reactor 21, compared with the existing integrated reactor, the present application is more portable in material taking and maintenance.

[0070] The present application adopts the combination of the jacking hydraulic cylinder 40 and the top ring 41 to drive the lifting of the reactor 20, the jacking force is large, the operation is stable and reliable, and the safety of the lifting process is ensured. The top ring 41 is composed of two bolt-connected half top rings, and the design that the top ring 41 is matched with the outer wall of the reactor 20 ensures that the force is evenly distributed during jacking, and facilitates installation and disassembly. The hydraulic lifting frame 4 and the jacking hydraulic cylinder 40 are electrically connected with the cefuroxime sodium production control system and can be synchronously elongated, so that the centralized automatic control of the lifting process of the reactor 20 is realized, and it is ensured that the output end of the standby liquid preparation kettle 1 is always connected with the reactor 20.

[0071] In the embodiment 1, the top of the reactor 20 is provided with a plurality of DCCF reactant feeding pipes 201 and a pressure detection gauge 202, the DCCF reactant feeding pipes 201 are used for the input of reactants in the DCCF solid powder preparation process, the pressure detection gauge 202 is used for detecting the pressure in the reactor 20, a mounting groove 203 is formed in the side wall of the reactor 20, a mounting window 204 is hingedly connected to the mounting groove 203, the mounting groove 203 is used for mounting a camera, and the bottom of the reactor 20 is provided with a DCCF solid powder output pipe 205.

[0072] The side wall of the reaction shell 3 is communicated with an external vacuum pump, a plurality of electromagnetic liquid discharge channels 206 are formed in the bottom of the reaction shell 3, a liquid discharge cavity 2060 is formed between the temperature control shell 30 and the heat preservation shell 31, two groups of liquid discharge connecting holes 2061 are formed in the bottom of the liquid discharge cavity 2060, and the two groups of liquid discharge connecting holes 2061 are both communicated with an external waste liquid collection bin.

[0073] Optionally, various sensors such as a PH sensor, a temperature sensor, and an ultrasonic drop speed sensor can also be mounted on the mounting groove 203.

[0074] In this embodiment, the electromagnetic drainage channel one 206 can adopt a corrosion-resistant diaphragm electromagnetic valve or a piston electromagnetic valve for controlling the automatic discharge of reaction waste liquid or washing liquid, and the DCCF solid powder output pipe 205 adopts a ball valve to control the on-off.

[0075] The working principle and beneficial effects of the above technical solutions are as follows:

[0076] The step of hydrolyzing 7-ACA to obtain 7-DACA by the reaction kettle one 20 includes: adding a designed amount of purified water and 7-ACA raw material into the reaction kettle one 20 through the DCCF reactant feeding pipe 201, starting the stirring action through the DCCF solid powder preparation assembly, and controlling the temperature at 0-5°C through the temperature control spiral pipe 33 to form a uniform suspension, slowly dropping 1 mol / L NaOH solution through the precision metering pump, monitoring and feedback controlling the dropping speed in real time through the online pH sensor, and strictly maintaining the reaction liquid pH=9-10, and reacting at 0-5°C for about 100 minutes, thereby completing the whole step of hydrolyzing 7-ACA to obtain 7-DACA.

[0077] The step of reacting the furanoyl chloride side chain acetone solution with 7-DACA to obtain DCCF solid powder includes: slowly dropping a proper amount of acetone and the furanoyl chloride side chain acetone solution prepared in the standby liquid preparation kettle 1 and 1 mol / L NaOH solution into the reaction kettle one 20 through the DCCF reactant feeding pipe 201, and the NaOH solution is used to maintain the pH=7.5-8, after the dropping is completed, the reaction is incubated at 0°C for 120 minutes through the temperature control spiral pipe 33, after the reaction is completed, 10-11 times the volume of low-temperature purified water is added into the reaction kettle one 20 to make the product DCCF precipitate, and the crystal is aged and grown under low-speed stirring for 120 minutes to improve the purity and filtration performance, then the DCCF precipitated in the reaction kettle one 20 is filtered, the filter cake is washed with purified water during the filtration process to remove inorganic salts and other water-soluble impurities, the filtrate flows into the drainage cavity one 2060 through the two groups of drainage connecting holes 2061, and then flows into the external waste liquid collection bin one, after the filtration is completed, the electromagnetic drainage channel one 206 is closed, then the external vacuum pump is started to vacuumize the reaction shell 3, and then the wet product DCCF is vacuum dried at 40°C through the auxiliary heating wire heating combined with the heat transfer of the temperature control spiral pipe 33.

[0078] This invention, by setting up multiple DCCF reactant feed pipes 201, can meet the precise and orderly addition of various materials such as 7-ACA, water, NaOH solution, acetic acid, and acetone. The pressure gauge 202 can monitor the pressure inside the reactor 20 in real time, providing data support for safe production. The design of the mounting groove 203 and mounting window 204 facilitates the installation of monitoring equipment such as cameras, pH sensors, and temperature sensors, realizing online real-time monitoring of key parameters of the reaction process. Based on the monitoring results, the reaction conditions can be precisely controlled to ensure product quality. The design of the electromagnetic drainage channel 206, drainage chamber 2060, and drainage connection hole 2061 realizes the efficient and closed collection and discharge of reaction waste liquid and washing liquid, avoiding cross-contamination and maintaining the cleanliness of the production environment.

[0079] Example 5: Based on Example 4, the DCCF solid powder preparation assembly includes a rotating shaft 200, which is driven by a rotating shaft drive assembly on the reactor 20. A meshing cylinder 2002 is fixedly connected to the rotating shaft 200. A discharge frustum 2003 is fixedly connected to the bottom of the meshing cylinder 2002, with the larger end of the discharge frustum 2003 at the top and the smaller end at the bottom. A stirring and filtering basket 2005 is slidably connected to the meshing cylinder 2002. The stirring and filtering basket 2005 includes a meshing part 2006 and a basket body 2007 fixedly connected to the meshing part 2006. The meshing cylinder 2002 has an opening... The reactor is provided with a meshing groove 2004, and a meshing block 2008 is fixedly connected to the inner wall of the meshing part 2006. The meshing block 2008 is slidably connected to the meshing groove 2004. The inner wall of the reaction shell 3 of the reactor 20 is provided with a basket lifting drive assembly. The working end of the basket lifting drive assembly is slidably connected to the annular groove 2009 of the basket 2007. The basket lifting drive assembly is used to drive the basket 2007 to move up and down. An electric collecting scraper 2015 is hinged to the inner wall of the reaction shell 3. The electric collecting scraper 2015 is used to scrape off the DCCF solid powder attached to the basket 2007.

[0080] In this embodiment, the shaft drive assembly includes a shaft drive motor 2000 and a reduction gearbox 2001. The reduction gearbox 2001 is fixedly connected to the reactor 20, and the shaft drive motor 2000 is fixedly connected to the reduction gearbox 2001. The output end of the shaft drive motor 2000 is connected to the input end of the reduction gearbox 2001, and the output end of the reduction gearbox 2001 is connected to the shaft 200 via a coupling.

[0081] The working principle and beneficial effects of the above technical solution are as follows:

[0082] The stirring action of the DCCF solid powder preparation assembly specifically includes: when the stirring action is performed, the basket lifting driving assembly controls the control position of the stirring filter basket 2005, so that the engaging block 2008 is slidingly connected in the engaging groove 2004, when the driving shaft one driving assembly drives the rotation of the driving shaft one 200, the stirring filter basket 2005 also rotates synchronously, thereby playing a stirring role. The lifting of the stirring filter basket 2005 by the basket lifting driving assembly can adjust the spatial position of the stirring filter basket 2005 in the reaction shell 3, so as to realize stirring at different spatial positions and speed up the stirring efficiency.

[0083] The filtering action of the DCCF solid powder preparation assembly specifically includes: 10-11 times the volume of low-temperature purified water is added to the reaction kettle one 20, so that the product DCCF is analyzed and discharged, and the crystal is aged for 120 minutes under low-speed stirring to make the crystal complete and grow. During the stirring process, the stirring filter basket 2005 moves upward synchronously and slowly, and the precipitated crystal is filtered into the basket 2007 because the particle size is greater than the corresponding hole diameter of the basket 2007. When the stirring filter basket 2005 moves to the uppermost position, the crystal filtered and accumulated in the stirring filter basket 2005 forms a filter cake. At this time, the filter cake is washed with purified water to remove inorganic salts and other water-soluble impurities. At the same time, the electromagnetic drainage channel one 206 is opened, the filtrate flows into the drainage cavity one 2060 through the electromagnetic drainage channel one 206, and then flows into the external waste liquid collection bin one through the two groups of drainage connecting holes 2061. After washing is completed and the filtrate is drained, the electromagnetic drainage channel one 206 is closed, the external vacuum pump is started, the reaction shell 3 is vacuumized, and then the wet product DCCF is vacuum dried at 40°C through the heating of the auxiliary heating wire of the reaction kettle one 20 and the heat transfer of the temperature control spiral pipe 33.

[0084] The solid powder collection action of the DCCF solid powder preparation assembly specifically includes: after drying is completed, the electric collection scraping strip 2015 is rotated from the initial recovery state, as shown in the state of Figure 4 , to the state of Figure 6 , the basket lifting driving assembly drives the basket 2007 to move upward until the electric collection scraping strip 2015 is attached to the inner wall of the basket 2007. Then, the driving shaft one 200 drives the rotation of the basket 2007. During the rotation of the basket 2007, the DCCF solid powder in the basket 2007 is loosened, so that the DCCF solid powder does not adhere to the basket 2007.

[0085] The specific steps of inputting the DCCF solid powder prepared by the reaction kettle one 20 into the reaction kettle two 21 include:

[0086] The basket lifting driving assembly drives the basket 2007 carrying the DCCF solid powder to move downward, and the rotating shaft one 200 is in a non-rotating state. When the engaging part 2006 of the stirring and filtering basket 2005 moves to the disengagement block 2008 from the engagement groove 2004, a gap begins to be generated between the engaging part 2006 and the discharging circular table 2003. At this time, the bottom of the engaging part 2006 moves to abut against the top of the DCCF solid powder output pipe 205. The electromagnetic valve in the DCCF solid powder output pipe 205 is opened at this time. The DCCF solid powder in the basket 2007 slides into the DCCF solid powder output pipe 205 under the action of gravity through the gap between the engaging part 2006 and the discharging circular table 2003, and is output to the reaction kettle two 21 by the DCCF solid powder output pipe 205. The gap size between the engaging part 2006 and the discharging circular table 2003 can be flexibly controlled by controlling the lifting of the stirring and filtering basket 2005, and the discharging on-off can be controlled. When the stirring and filtering basket 2005 moves upward to the engagement groove 2004 again, the DCCF solid powder stops discharging, and the discharging speed can be adjusted by adjusting the gap size between the engaging part 2006 and the discharging circular table 2003.

[0087] The DCCF solid powder preparation assembly integrates the functions of stirring, filtering and solid powder collecting, and has a simple structure. The stirring and filtering integration can be realized by the design of the stirring and filtering basket 2005, without additional design of a stirring paddle.

[0088] The stirring, filtering and crystal collecting functions are creatively integrated on the single component of the stirring and filtering basket 2005. Through the combination of lifting and rotating movements, all post-processing procedures of reaction stirring, crystal growing, filtering, washing, vacuum drying and solid product discharging are sequentially completed. The structure is compact, the functions are highly integrated, the device structure is significantly simplified, the manufacturing cost is reduced, the height of the stirring and filtering basket 2005 is accurately controlled by the basket lifting driving assembly, the stirring of different depths of the reaction system can be realized to strengthen the mass transfer, the filtering time and the discharging rate and on-off of the dried solid product after drying can be accurately controlled, and the operation is flexible and accurate. The electric collecting scraper 2015 is arranged, which can effectively scrape off the dried solid powder attached to the inner wall of the basket 2007, solves the industry problem that the solid material is easy to stick to the wall and the discharging is not complete in the filtering and drying integrated equipment, and ensures the complete recovery of the product and the self-cleaning ability of the equipment.

[0089] In the embodiment 6, the basket lifting driving assembly comprises two groups of symmetrical electric lead screws 2010, the electric lead screws 2010 are rotationally connected in the lead screw mounting cavities 2011 in the reaction shell 3, lifting nuts 2012 are threadedly connected on the electric lead screws 2010, micro guide blocks 2013 and T-shaped connecting blocks 2014 are fixedly connected on the lifting nuts 2012, the micro guide blocks 2013 are slidably connected in the lead screw mounting cavities 2011 at the ends away from the lifting nuts 2012, and the T-shaped connecting blocks 2014 are slidably connected in the annular sliding grooves 2009 at the ends away from the lifting nuts 2012.

[0090] The basket lifting driving assembly works as follows: when the basket lifting driving assembly works, the electric lead screws 2010 rotate to drive the lifting nuts 2012 to move up and down, the lifting nuts 2012 move up and down to drive the basket 2007 to move up and down through the T-shaped connecting blocks 2014, and the T-shaped connecting blocks 2014 move up and down without interfering with the rotation of the basket 2007 with the rotating shaft 1 200 due to the sliding connection of the T-shaped connecting blocks 2014 in the annular sliding grooves 2009 at the ends away from the lifting nuts 2012.

[0091] The transmission mode of the electric lead screws 2010 and the lifting nuts 2012 is adopted, the transmission precision is high, the positioning is accurate, the precise control of the position of the stirring and filtering basket 2005 can be realized, the sliding connection of the T-shaped connecting blocks 2014 and the annular sliding grooves 2009 is designed, the lifting driving and the rotating movement of the basket 2007 are decoupled, the basket 2007 can rotate freely without interfering with the lifting movement, the normal operation of the stirring function is realized, the structure design is ingenious, and the operation is reliable.

[0092] In the embodiment 7, the reaction kettle two 21 comprises a plurality of cefuroxime sodium reactant feeding pipes 210 and a pressure detection meter two, the cefuroxime sodium reactant feeding pipes 210 are used for inputting reactants in the preparation process of cefuroxime sodium, the pressure detection meter two is used for detecting the pressure in the reaction kettle two 21, the reaction shell 3 of the reaction kettle two 21 is communicated with an ice water supply cylinder 211, a plurality of electromagnetic liquid discharge passages two 212 are arranged at the bottom of the reaction shell 3 of the reaction kettle two 21, a liquid discharge cavity two 213 is formed between the temperature control shell 30 of the reaction kettle two 21 and the heat preservation shell 31 of the reaction kettle two 21, a waste pipe 2120 is arranged at the bottom of the heat preservation shell 31 of the reaction kettle two 21, and the waste pipe 2120 is communicated with an external waste liquid collection bin two at the end away from the heat preservation shell 31 of the reaction kettle two 21.

[0093] The reaction kettle two 21 is rotationally connected with a rotating shaft two 214, the rotating shaft two 214 is driven by a rotating shaft two driving assembly, the rotating shaft two 214 is fixedly connected with a liquid discharge cavity scraping strip 215, the liquid discharge cavity scraping strip 215 is rotationally connected in the liquid discharge cavity two 213, the rotating shaft two 214 is fixedly connected with two symmetrical meshing guide strips 216, the rotating shaft two 214 is slidably connected with a cefuroxime sodium filter screen assembly, the cefuroxime sodium filter screen assembly comprises a cefuroxime sodium filter screen 217 and a meshing sliding sleeve 218, the inner wall of the meshing sliding sleeve 218 is slidably connected with the meshing guide strips 216 on the rotating shaft two 214 in cooperation with each other, the cefuroxime sodium filter screen 217 is fixedly connected with the meshing sliding sleeve 218, and the cefuroxime sodium filter screen 217 is fixedly connected with an auxiliary stirring paddle 219.

[0094] The reaction kettle two 21 further comprises a DCCF acetonitrile reaction liquid preparation cylinder 22, the DCCF acetonitrile reaction liquid preparation cylinder 22 is rotationally connected with the DCCF solid powder output pipe 205 of the reaction kettle one 20, and the DCCF acetonitrile reaction liquid preparation cylinder 22 is used for preparing a DCCF acetonitrile reaction liquid.

[0095] In the embodiment, the rotating shaft two driving assembly comprises a rotating shaft two driving motor 2140, the rotating shaft two driving motor 2140 is fixedly connected with the bottom of the heat preservation shell 31 of the reaction kettle two 21, the output end of the rotating shaft two driving motor 2140 is fixedly connected with a bevel gear one 2141, the rotating shaft two 214 is fixedly connected with a bevel gear two 2142, and the bevel gear two 2142 is meshed with the bevel gear one 2141.

[0096] In the embodiment, the electromagnetic valve in the electromagnetic liquid discharge channel two 212 can adopt a corrosion-resistant diaphragm type electromagnetic valve or a piston type electromagnetic valve, and is used for controlling automatic discharge of reaction waste liquid or washing liquid.

[0097] The working principle and beneficial effects of the above technical solution are as follows: during work, the DCCF acetonitrile reaction liquid preparation cylinder 22 prepares the DCCF acetonitrile reaction liquid, at the same time, the ice water supply cylinder 211 pumps a large amount of ice water into the reaction shell 3 of the reaction kettle two 21, after the preparation of the DCCF acetonitrile reaction liquid is completed, the electromagnetic valve at the bottom of the DCCF acetonitrile reaction liquid preparation cylinder 22 is opened to pour the DCCF acetonitrile reaction liquid into the reaction shell 3 of the reaction kettle two 21 containing a large amount of ice water, then the shaft two driving assembly drives the shaft two 214 to rotate to drive the meshing sliding sleeve 218 to rotate, thereby driving the cefuroxime sodium filter screen 217 and the auxiliary stirring paddle 219 to rotate synchronously, and stirring is realized at room temperature, during which NaOH solution is added to adjust pH=2-3, and ethyl acetate is added for extraction, and the organic phase is combined, then activated carbon is used for decolorization treatment, then sodium lactate, sodium acetate and anhydrous ethanol solution are added to the decolorized organic phase, and the cefuroxime sodium filter screen 217 and the auxiliary stirring paddle 219 are stirred uniformly to make the cefuroxime sodium precipitate on the cefuroxime sodium filter screen 217, after the precipitation is completed, the bottom of the reaction shell 3 of the reaction kettle two 21 is opened, the filtrate flows into the drainage cavity two 213, and finally is discharged to the outside waste liquid collection bin through the drainage cavity two 213 and the waste pipe 2120, during which a mixed solution of tetrahydrofuran and ethanol is added to the reaction shell 3 of the reaction kettle two 21 to wash the precipitated cefuroxime sodium, after the washing is completed, the reaction shell 3 of the reaction kettle two 21 is vacuumized by an external vacuum pump, then the auxiliary heating wire of the reaction kettle two 21 is heated to cooperate with the heat transfer of the temperature control spiral pipe 33 to realize vacuum drying of the wet product DCCF at 40 DEG C, and after vacuum drying, cefuroxime sodium light yellow solid powder is obtained, then the reaction kettle one 20 is lifted up by the auxiliary lifting assembly, a material taking opening is formed between the reaction kettle one 20 and the reaction kettle two 21, and the staff takes out the cefuroxime sodium filter screen assembly with cefuroxime sodium adhered thereon along the shaft two 214 from the material taking opening.

[0098] The design of the ice water supply cylinder 211 of the application ensures that a large amount of ice water required for the hydrolysis quenching step can be quickly put into the reaction kettle two 21, and the reaction heat can be absorbed in time to ensure the safety of operation; the cefuroxime sodium filter screen assembly is slidably arranged on the shaft two 214, so that it can be used as a stirring paddle to promote reaction mixing and extraction, and can also be used as a filter screen to intercept the precipitated cefuroxime sodium crystals, one thing with two uses, which simplifies the internal structure; the drainage cavity scraping strip 215 can clean the solid residues that may be deposited in the drainage cavity two 213 in time to prevent clogging and ensure smooth drainage; the DCCF acetonitrile reaction liquid preparation cylinder 22 is specially arranged to prepare a suspension of DCCF solid powder and anhydrous acetonitrile in a closed environment, and then the suspension is put into the ice water environment of the reaction kettle two 21 for hydrolysis, which perfectly solves the problem of safe and efficient switching from a water-free environment to a water-containing environment.

[0099] Example 8: On the basis of example 7, the DCCF acetonitrile reaction liquid preparation cylinder 22 comprises a preparation cylinder body 220, which is rotationally connected to the DCCF solid powder output pipe 205 of the reaction kettle one 20, the DCCF solid powder output pipe 205 is communicated with the external acetonitrile supply end through the acetonitrile supply port 224, the bottom of the preparation cylinder body 220 is provided with a cylinder meshing groove 221, which is used for mutual cooperation with the rotating shaft two 214 and the meshing guide strip 216; the bottom of the preparation cylinder body 220 is provided with a plurality of electromagnetic drainage passages three 222, and the inner wall of the preparation cylinder body 220 is fixedly connected with a fixed stirring paddle 223.

[0100] In this embodiment, the electromagnetic valve in the electromagnetic drainage passage three 222 can adopt a corrosion-resistant diaphragm type electromagnetic valve or a piston type electromagnetic valve, which is used for controlling the automatic discharge of the DCCF acetonitrile reaction liquid.

[0101] The working principle and beneficial effects of the above technical scheme are as follows: when the DCCF acetonitrile reaction liquid is prepared, the external acetonitrile supply end passes through the acetonitrile supply port 224 and the DCCF solid powder output pipe 205 to introduce a predetermined amount of anhydrous acetonitrile into the preparation cylinder body 220, so as to ensure that the temperature is 0-5℃, then the DCCF solid powder is output from the DCCF solid powder output pipe 205 to the preparation cylinder body 220 under the action of gravity and is suspended in acetonitrile, the rotating shaft two 214 is rotated, and the preparation cylinder body 220 is driven to rotate under the action of the meshing guide strip 216 and the cylinder meshing groove 221, the fixed stirring paddle 223 of the preparation cylinder body 220 can play a stirring role in the rotating process of the preparation cylinder body 220, and finally the DCCF acetonitrile reaction liquid is formed, then the electromagnetic valve in the electromagnetic drainage passage three 222 is opened, and the DCCF acetonitrile reaction liquid is poured into the reaction shell 3 of the reaction kettle two 21 containing a large amount of ice water for the preparation of cefuroxime sodium.

[0102] The design of the cylinder meshing groove 221 and the meshing guide strip 216 on the rotating shaft two 214 makes the preparation cylinder body 220 not only be driven to rotate, but also be easily separated; the fixed stirring paddle 223 can effectively stir the internal material when the preparation cylinder body 220 rotates, so as to promote the uniform suspension of the DCCF solid in acetonitrile; the electromagnetic drainage passage three 222 realizes the rapid and controllable discharge of the prepared reaction liquid, which provides guarantee for the timely performance of the subsequent reaction.

[0103] Example 9: On the basis of example 1, a reaction device for the production of cefuroxime sodium further comprises:

[0104] The component monitoring module comprises a spectrum probe arranged in the interior of the first reaction kettle 20 and the second reaction kettle 21, and the spectrum probe is used for collecting original spectrum signals of materials in the corresponding reaction kettle in real time, wherein the two spectrum probes are respectively arranged on the side walls of the first reaction kettle 20 and the second reaction kettle 21, and both of them are used for obtaining the original spectrum signals of materials in the corresponding reaction kettle by non-contact measurement;

[0105] The data analysis module is used for receiving the original spectrum signals of materials in the first reaction kettle 20 and the second reaction kettle 21, and inputting the original spectrum signals into the trained concentration determination model to obtain the concentration data of at least one key component in the corresponding reaction system of the first reaction kettle 20 and the second reaction kettle 21;

[0106] The feedback execution module is used for comparing the concentration data of at least one key component in the corresponding reaction system of the first reaction kettle 20 and the second reaction kettle 21 with the preset process standard value, and generating a control instruction to dynamically adjust the execution components of the first reaction kettle 20 and the second reaction kettle 21 so as to make the reaction process meet the preset process trajectory.

[0107] In this embodiment, the trained concentration determination model comprises model one, model two, model three and model four, the model one, the model two, the model three and the model four are respectively obtained by training the neural network model with the spectrum data collected in the 7-ACA hydrolysis, the DCCF amidation reaction, the carbamoylation reaction and the crystallization of cefuroxime sodium as input quantities, and with the concentration data of the key components corresponding to the 7-ACA hydrolysis, the DCCF amidation reaction, the carbamoylation reaction and the crystallization of cefuroxime sodium as output quantities.

[0108] In this embodiment, the key components corresponding to the 7-ACA hydrolysis, the DCCF amidation reaction, the carbamoylation reaction and the crystallization of cefuroxime sodium are "7-ACA and 7-DACA", "7-DACA and DCCF", "chlorosulfonic acid intermediate and carbamoylation product" and "cefuroxime acid" respectively, and the execution components corresponding to the 7-ACA hydrolysis, the DCCF amidation reaction, the carbamoylation reaction and the crystallization of cefuroxime sodium are "NaOH solution metering pump and corresponding temperature control system", "furanoyl chloride side chain acetone solution metering pump, NaOH solution metering pump and corresponding temperature control system", "corresponding temperature control system" and "sodium lactate / acetic acid solution metering pump and corresponding temperature control system" respectively.

[0109] The working principle and beneficial effects of the above technical solution are as follows:

[0110] The spectral probes inside reactor 20 and reactor 21 are used to monitor the hydrolysis of 7-ACA, the amidation reaction of DCCF, the carbamylation reaction, and the crystallization process of cefuroxime sodium in real time. Taking the amidation reaction in reactor 20 as an example, the process includes: the spectral probe continuously acquiring the spectral signal of the amidation reaction in reactor 20 and transmitting the data to the data analysis module. Model 2 of the data analysis module outputs the concentration data of 7-DACA in the current reaction solution and transmits the concentration data of 7-DACA in the current reaction solution to the feedback execution module. The PLC controller in the feedback execution module compares the concentration of 7-DACA in the current reaction solution with the preset process standard curve, i.e., the ideal concentration-time relationship. If the concentration of 7-DACA in the current reaction solution is lower than the ideal concentration, it indicates that the reaction rate is too fast. The PLC generates control instructions to dynamically reduce the dropping rate of the acetone solution metering pump for furanyl chloride side chain. At the same time, the reaction temperature can also be finely adjusted to stabilize the reaction temperature in the optimal range.

[0111] Example 10: Based on Example 5, at least one ultrasonic transducer array is installed on the basket 2007.

[0112] The working principle and beneficial effects of the above technical solution are as follows: When DCCF crystals are filtered in the basket 2007 to form a filter cake and are subsequently vacuum dried, the ultrasonic generator is activated, driving the ultrasonic transducer array to work in a high-frequency, low-amplitude mode. The generated micro-vibrations are transmitted to the entire filter cake through the mesh wall of the basket 2007, greatly reducing the adhesion between the filter cake and the mesh wall, preventing DCCF microcrystalline particles from embedding into the filter mesh pores, maintaining the high permeability of the filter mesh, significantly shortening the filtration and drying time, keeping the filter cake structure loose, providing better heat conduction and steam dissipation channels for subsequent vacuum drying, improving drying efficiency, and avoiding product degradation caused by local overheating. When drying is completed and the DCCF solid powder needs to be discharged through the DCCF solid powder output pipe 205, the control system switches the ultrasonic generator to a low-frequency, high-amplitude pulse working mode. The powerful vibration energy can effectively destroy the electrostatic force and friction between powder particles, ensuring the continuous, stable, and smooth discharge of DCCF solid powder.

[0113] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.

Claims

1. A reaction apparatus for the production of cefuroxime sodium, characterized in that: It includes a standby solution preparation vessel (1) and a cefuroxime sodium preparation vessel (2). The cefuroxime sodium preparation vessel (2) is connected to the output end of the standby solution preparation vessel (1). The standby solution preparation vessel (1) is used to prepare an acetone solution with furanyl chloride side chain. The cefuroxime sodium preparation vessel (2) includes a first reaction vessel (20) and a second reaction vessel (21). The second reaction vessel (21) and the first reaction vessel (20) are connected by an auxiliary lifting assembly. The auxiliary lifting assembly is used to drive the first reaction vessel (20) to move up and down relative to the second reaction vessel (21). The first reaction vessel (20) is used to hydrolyze 7-DACA with 7-ACA as the starting reactant, and obtain DCCF solid powder by reacting with acetone solution of furanyl chloride side chain. The DCCF solid powder is then output to the second reaction vessel (21). The second reaction vessel (21) is used to carbamate the 3-hydroxymethyl group of DCCF to obtain cefuroxime acid, and perform sodium conversion operation to obtain cefuroxime sodium. The shells of reactor one (20) and reactor two (21) are, from the inside to the outside, a reaction shell (3), a temperature control shell (30) and a heat preservation shell (31). A temperature control spiral tube (33) is arranged in the temperature control cavity (32) between the inner wall of the temperature control shell (30) and the outer wall of the reaction shell (3). The temperature control spiral tube (33) forms a circuit with the external temperature control medium supply end. An auxiliary heating wire is integrated in the temperature control shell (30). The reactor (20) is equipped with a DCCF solid powder preparation component. The DCCF solid powder preparation component is used for stirring, filtering and collecting solid powder in the DCCF solid powder preparation process. The DCCF solid powder preparation component includes a rotating shaft (200). The rotating shaft (200) is driven by a rotating shaft drive component on the reactor (20). A meshing cylinder (2002) is fixedly connected to the rotating shaft (200). A discharge frustum (2003) is fixedly connected to the bottom of the meshing cylinder (2002). The large end of the discharge truncated cone (2003) is on top and the small end is on the bottom. The meshing cylinder (2002) is slidably connected to the stirring and filtering basket (2005). The stirring and filtering basket (2005) includes a meshing part (2006) and a basket body (2007) fixedly connected to the meshing part (2006). The meshing cylinder (2002) is provided with a meshing groove (2004). A meshing block (2008) is fixedly connected to the inner wall of the meshing part (2006). The meshing block (2008) is slidably connected to the meshing groove (2004).

2. The reaction apparatus for the production of cefuroxime sodium according to claim 1, characterized in that: An electric stirring paddle is rotatably connected inside the standby liquid preparation vessel (1). A feeding cover (10) is rotatably connected to the feeding port of the standby liquid preparation vessel (1). The feeding port is used to add furan ammonium salt. Liquid delivery pipe one (11), liquid delivery pipe two (12), and liquid delivery pipe three (13) are connected to the standby liquid preparation vessel (1). Liquid delivery pipe one (11) is connected to the benzene supply end and is used to deliver benzene to the standby liquid preparation vessel (1). Liquid delivery pipe two (12) is connected to the oxalyl chloride and benzene mixed solution supply end and is used to deliver benzene to the standby liquid preparation vessel (1). A mixture of oxalyl chloride and benzene is supplied to the standby liquid preparation vessel (1). The liquid supply pipe three (13) is connected to the acetone supply end and is used to supply acetone to the standby liquid preparation vessel (1). A catalyst connection port (14) is fixedly connected to the standby liquid preparation vessel (1). The catalyst connection port (14) is used to connect to the dimethylacetamide supply end. A furanyl chloride side chain guide pipe (15) is provided at the bottom of the standby liquid preparation vessel (1). The furanyl chloride side chain guide pipe (15) is connected to the top of the reaction vessel one (20).

3. The reaction apparatus for the production of cefuroxime sodium according to claim 1, characterized in that: The auxiliary lifting assembly includes two symmetrically arranged lifting hydraulic cylinders (40) and a top ring (41). Both lifting hydraulic cylinders (40) are bolted to the outer wall of the second reactor (21). The output ends of both lifting hydraulic cylinders (40) are fixedly connected to the bottom of the top ring (41). An annular vessel waist (34) is fixedly connected to the first reactor (20). The top of the top ring (41) is used to abut against the bottom surface of the annular vessel waist (34), thereby lifting the first reactor (20) upward under the action of the lifting hydraulic cylinders (40). The standby liquid preparation vessel (1) is installed on the hydraulic lifting frame (4). The hydraulic lifting frame (4) and the lifting hydraulic cylinder (40) are electrically connected to the cefuroxime sodium production control system. The cefuroxime sodium production control system can control the hydraulic lifting frame (4) and the lifting hydraulic cylinder (40) to extend and retract synchronously.

4. The reaction apparatus for the production of cefuroxime sodium according to claim 1, characterized in that: The top of the reactor (20) is equipped with several DCCF reactant feed pipes (201) and a pressure gauge (202). The DCCF reactant feed pipes (201) are used for inputting reactants during the preparation of DCCF solid powder. The pressure gauge (202) is used to detect the pressure inside the reactor (20). The side wall of the reactor (20) is provided with an installation groove (203). The installation groove (203) is hinged to an installation window (204). The installation groove (203) is used to install a camera. The bottom of the reactor (20) is provided with a DCCF solid powder output pipe (205). The side wall of the reaction shell (3) of the reactor (20) is connected to the external vacuum pump. Several electromagnetic drainage channels (206) are opened at the bottom of the reaction shell (3) of the reactor (20). A drainage chamber (2060) is formed between the temperature control shell (30) of the reactor (20) and the heat preservation shell (31) of the reactor (20). Two sets of drainage connection holes (2061) are opened at the bottom of the drainage chamber (2060). Both sets of drainage connection holes (2061) are connected to the external waste liquid collection chamber.

5. A reaction apparatus for the production of cefuroxime sodium according to claim 4, characterized in that: The inner wall of the reaction shell (3) of the reactor (20) is provided with a basket lifting drive assembly. The working end of the basket lifting drive assembly is slidably connected in the annular groove (2009) of the basket (2007). The basket lifting drive assembly is used to drive the basket (2007) to move up and down. The inner wall of the reaction shell (3) of the reactor (20) is hinged with an electric collecting scraper (2015), which is used to scrape off the DCCF solid powder attached to the basket (2007).

6. A reaction apparatus for the production of cefuroxime sodium according to claim 5, characterized in that: The basket lifting drive assembly includes two sets of symmetrically arranged electric screws (2010). The electric screws (2010) are rotatably connected to the screw mounting cavity (2011) inside the reaction shell (3) of the reactor (20). The electric screws (2010) are threaded with lifting nuts (2012). The lifting nuts (2012) are fixedly connected with miniature guide blocks (2013) and T-shaped connecting blocks (2014). The end of the miniature guide block (2013) away from the lifting nut (2012) is slidably connected up and down in the screw mounting cavity (2011). The end of the T-shaped connecting block (2014) away from the lifting nut (2012) is slidably connected in the annular groove (2009).

7. A reaction apparatus for the production of cefuroxime sodium according to claim 1, characterized in that: Reactor 2 (21) includes several cefuroxime sodium reactant feed pipes (210) and pressure gauge 2. The cefuroxime sodium reactant feed pipes (210) are used for inputting reactants during the preparation of cefuroxime sodium, and the pressure gauge 2 is used to detect the pressure inside reactor 2 (21). The reaction shell (3) of reactor 2 (21) is connected to an ice water supply cylinder (211). Several electromagnetic drainage channels 2 are provided at the bottom of the reaction shell (3) of reactor 2 (21). (212) A second drain chamber (213) is formed between the temperature control shell (30) of the second reactor (21) and the heat insulation shell (31) of the second reactor (21). A waste discharge pipe (2120) is provided at the bottom of the heat insulation shell (31) of the second reactor (21). The end of the waste discharge pipe (2120) away from the heat insulation shell (31) of the second reactor (21) is connected to the external waste liquid collection chamber 2. The side wall of the reaction shell (3) of the second reactor (21) is connected to the external vacuum pump. Rotary shaft 2 (214) is rotatably connected inside reactor 2 (21). Rotary shaft 2 (214) is driven by rotating shaft 2 drive assembly. Drainage chamber scraper (215) is fixedly connected to rotating shaft 2 (214). Drainage chamber scraper (215) is rotatably connected inside drainage chamber 2 (213). Two symmetrically arranged meshing guide bars (216) are fixedly connected to rotating shaft 2 (214). Cefuroxime sodium filter assembly is slidably connected to rotating shaft 2 (214). Cefuroxime sodium filter assembly includes cefuroxime sodium filter (217) and meshing sleeve (218). The inner wall of meshing sleeve (218) cooperates with meshing guide bar (216) and is slidably connected to rotating shaft 2 (214). Cefuroxime sodium filter (217) is fixedly connected to meshing sleeve (218). Auxiliary stirring paddle (219) is fixedly connected to cefuroxime sodium filter (217). The second reactor (21) also includes a DCCF acetonitrile reaction solution preparation cylinder (22), which is rotatably connected to the DCCF solid powder output pipe (205) of the first reactor (20). The DCCF acetonitrile reaction solution preparation cylinder (22) is used to prepare DCCF acetonitrile reaction solution.

8. A reaction apparatus for the production of cefuroxime sodium according to claim 7, characterized in that: The DCCF acetonitrile reaction solution preparation cylinder (22) includes a preparation cylinder body (220), which is rotatably connected to the DCCF solid powder output pipe (205) of the first reactor (20). The DCCF solid powder output pipe (205) is connected to the external acetonitrile supply end through the acetonitrile supply port (224). A cylinder engagement groove (221) is provided at the bottom of the preparation cylinder body (220). The cylinder engagement groove (221) is used to cooperate with the second rotating shaft (214) and the engagement guide bar (216). The bottom of the preparation cylinder (220) is provided with several electromagnetic drainage channels (222), and a fixed stirring paddle (223) is fixedly connected to the inner wall of the preparation cylinder (220).

9. A reaction apparatus for the production of cefuroxime sodium according to claim 1, characterized in that: Also includes: The component monitoring module includes a spectral probe installed inside reactor one (20) and reactor two (21). The spectral probe is used to collect the original spectral signals of the corresponding materials in the reactor in real time. The data analysis module is used to receive the original spectral signals of the materials in reactor 1 (20) and reactor 2 (21) and input them into the trained concentration determination model to obtain the concentration data of at least one key component in the reaction system corresponding to reactor 1 (20) and reactor 2 (21); The feedback execution module is used to compare the concentration data of at least one key component in the reaction system corresponding to reactor one (20) and reactor two (21) with the preset process standard value, and generate control commands to dynamically adjust the execution components of reactor one (20) and reactor two (21) so that the reaction process conforms to the preset process trajectory.

10. A reaction apparatus for the production of cefuroxime sodium according to claim 5, characterized in that: At least one ultrasonic transducer array is installed on the basket (2007).

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