Production process and production system for erlotinib intermediate

Abstract

The invention discloses a production process for an erlotinib intermediate, which comprises the following steps: S1, condensation reaction: adding triethylamine, 2-methylbutynol and purified water into a condensation reaction kettle in sequence; 3-bromonitrobenzene and a mixed solution mixed with purified water, cuprous iodide, dichloro-bis (triphenylphosphine) palladium and triphenylphosphine are put from a manhole, the charging coefficient is 70%, and a heat preservation reaction is performed; after the reaction is finished, circulating water is introduced for cooling and layering, organic matters on the upper layer are transferred to a concentration reaction kettle, and triethylamine is subjected to reduced pressure distillation until no solvent flows out, namely an M15Z0 concentrated solution; after the condensation reaction, the water phase in the condensation reaction kettle is transferred into the triethylamine recovery kettle, stirring is performed, 30% of liquid caustic soda is added for neutralization, layered distillation is performed, and the distilled triethylamine liquid is obtained, so that the raw material triethylamine can be recovered and reused, and the waste of the raw material can be reduced.

Description

Technical Field

[0001] The present invention relates to the technical field of erlotinib intermediate production, and in particular to a production process and a production system for an erlotinib intermediate. Background Art

[0002] The reaction equation for producing erlotinib intermediate M15 is:

[0003] ①Condensation reaction

[0004] Main reaction:

[0005]

[0006] Side effects:

[0007]

[0008] Triethylamine recovery:

[0009]

[0010] ② Reduction reaction

[0011] Main reaction:

[0012]

[0013] ③ Elimination reaction Main reaction:

[0014] Side effects:

[0015]

[0016]

[0017] The existing production system lacks effective design for the recovery of important raw materials such as triethylamine. In the production process of erlotinib intermediates, triethylamine is a commonly used solvent and reactant, but the existing system cannot efficiently recover and reuse it, which not only increases production costs but also pollutes the environment. Summary of the invention

[0018] In order to solve the problems mentioned in the above background technology, the present invention provides a production process and a production system for an erlotinib intermediate.

[0019] In order to achieve the above object, the present invention adopts the following technical solutions:

[0020] A process for producing an erlotinib intermediate comprises the following steps:

[0021] S1: Condensation reaction

[0022] In the condensation reaction kettle, triethylamine, 2-methylbutynol and purified water are injected in order. 3-bromonitrobenzene and a mixed solution of (purified water, cuprous iodide, dichloro-bis(triphenylphosphine)palladium, triphenylphosphine) are added from the manhole, with a loading factor of 70%, and the reaction is kept warm;

[0023] After the reaction is completed, circulating water is passed to cool down and separate the layers, and the upper organic matter is moved to a concentration reactor, and triethylamine is distilled under reduced pressure until no solvent flows out, i.e., M15Z0 concentrated solution;

[0024] The aqueous phase is transferred to a triethylamine recovery kettle, stirred and neutralized by adding 30% liquid alkali, and distilled in layers to remove the triethylamine liquid;

[0025] S1: Reduction reaction

[0026] Put 95% ethanol and drinking water into the reduction kettle, and then put ammonium chloride into the manhole. After starting the stirring, slowly put the iron powder into the reduction kettle from the solid feeder;

[0027] Heat preservation reaction: raise the temperature, slowly add the ethanol solution containing M15Z0 to the reduction kettle, wash the storage tank and pipeline with ethanol after the addition is complete, keep warm, and take samples after the reaction is complete;

[0028] After the reaction is completed, the filtrate is filtered through a filter, the filtrate is concentrated under reduced pressure, the concentrate is evaporated with toluene, and then crystallized and centrifuged to obtain a wet product of M15Z1, and the wet product is dried under reduced pressure to obtain the product M15Z1;

[0029] S3: Elimination reaction

[0030] Put M15Z1 into the elimination kettle in batches, add toluene and potassium hydroxide, stir, control the temperature at 85-90°C, react for 1.5-3 hours, after the reaction is completed, filter press, pass the filtrate into the washing and stratification kettle, add drinking water for washing and stratification, drop 30% hydrochloric acid into the oil phase to adjust the pH value of the reaction system, extract and stratify, add dichloromethane into the aqueous phase, drop 30% liquid alkali, stir, confirm that the pH value remains unchanged, dry the organic phase with anhydrous sodium sulfate, filter press with nitrogen to the concentration kettle, control the temperature and reduce the pressure to concentrate to dryness, the concentrate in the kettle is 3-aminophenylacetylene (M15 crude product);

[0031] S4: Refining reaction

[0032] The crude M15 is subjected to thin film distillation and molecular distillation to obtain the finished product M15.

[0033] A production system for erlotinib intermediates, comprising a condensation reaction kettle, a concentration reaction kettle, a triethylamine recovery kettle, a condenser and a tail gas absorber, a reduction kettle, an elimination kettle, a washing and layering kettle, a thin film evaporator and a molecular distiller;

[0034] The exhaust port of the triethylamine recovery kettle is connected to the shell side of the condenser, the tail gas discharge port of the condenser is connected to the air inlet pipe of the tail gas absorber, the outside of the triethylamine recovery kettle is provided with a cold and hot medium coil, and the top of the tail gas absorber is also provided with a tail gas outlet.

[0035] Preferably, a stirrer is installed in the triethylamine recovery kettle, and the stirrer is driven to rotate by a first rotating motor.

[0036] Preferably, a discharge port is provided at the bottom end of the triethylamine recovery kettle, a liquid separation observer is installed on the discharge port, and a transparent observation window is provided on the liquid separation observer.

[0037] Preferably, a vertically arranged gas guide pipe is rotatably installed in the exhaust gas absorber, the gas guide pipe is connected to the intake pipe through a rotating joint, the gas guide pipe is driven to rotate by a second rotating motor, and a gas distribution mechanism is provided at the bottom end of the gas guide pipe.

[0038] Preferably, the gas distribution mechanism includes multiple mounting brackets, a gas distribution box is fixed on the top of the mounting bracket, the gas distribution box is connected to the gas guide pipe via a connecting pipe, a plurality of vertical branch pipe inlet pipes are rotatably installed on the top of the gas guide pipe, a plurality of horizontal branch pipes are fixed on the outside of the vertical branch pipes, and a gas outlet is opened on the horizontal branch pipes.

[0039] Preferably, a first spur gear is fixed to the outside of the vertical branch pipe, a second spur gear is rotatably installed between adjacent first spur gears on the gas distribution box, the first spur gear and the second spur gear are meshed in sequence, a gear ring is fixed to the top inner wall of the exhaust gas absorber through a bracket, and the first spur gear closest to the gas guide pipe is meshed with the gear ring.

[0040] Preferably, a threaded rod is rotatably installed on the side of the mounting bracket away from the gas distribution box, a threaded sleeve is installed on the external thread of the threaded rod, the threaded sleeve is horizontally movably installed on the mounting bracket through a guide mechanism, and a first magnet is fixed on the threaded sleeve, the first magnet is movably contacted with the surface of the gas distribution box, and a second magnet is movably installed on the inner wall of the gas distribution box through a guide rail, the first magnet and the second magnet attract each other, and a lifting plug is movably installed in the gas distribution box, the lifting plug is made of magnetic metal, and the lifting plug corresponds to the vertical branch pipe.

[0041] Preferably, a first bevel gear is fixed to one end of the threaded rod, a vertically arranged transmission rod is rotatably mounted on the mounting bracket, one end of the transmission rod is fixed to the second bevel gear, and the second bevel gear is meshed with the first bevel gear.

[0042] Preferably, a third spur gear is fixed to the other end of the transmission rod, a fourth spur gear is fixed to the inner wall of the bottom end of the exhaust gas absorber, and the fourth spur gear is meshed with the third spur gear.

[0043] Compared with the prior art, the present invention has the following beneficial effects:

[0044] 1. After the condensation reaction, the water phase in the condensation reaction kettle is transferred to a triethylamine recovery kettle, stirred and neutralized by adding 30% liquid alkali, and distilled in layers. The distilled triethylamine liquid can be used to recover the raw material triethylamine, which can be used again, thereby reducing the waste of raw materials;

[0045] 2. By adding a tail gas absorber at the tail gas discharge end of the condenser, the tail gas generated during the triethylamine recovery process can be effectively treated to reduce environmental pollution. The tail gas enters the gas guide pipe through the air inlet pipe, and the gas guide pipe can guide the tail gas to the bottom of the absorption liquid, and disperse it through the gas distribution mechanism to fully contact with the absorption liquid, thereby greatly improving the absorption effect of organic gas in the tail gas;

[0046] 3. The gas distribution mechanism includes multiple mounting brackets, gas distribution boxes, vertical branch pipes, horizontal branch pipes and other components. When the gas guide pipe rotates, it can drive the gas distribution box to rotate accordingly, thereby continuously changing the positions of the vertical branch pipes and horizontal branch pipes during the exhaust process. This dynamic distribution method further improves the distribution effect of the gas in the absorption liquid, allowing the exhaust gas to contact the absorption liquid more evenly, thereby improving the absorption efficiency;

[0047] 4. When the gas guide pipe rotates, since the gear ring is stationary, one of the first spur gears will rotate while moving around the gear ring, and then through the transmission of the second spur gear, it drives multiple first spur gears to rotate synchronously, and then drives multiple vertical branch pipes to rotate synchronously. This not only further improves the gas distribution effect, but also drives the horizontal branch pipes to stir the absorption liquid, making the concentration of the absorption liquid more uniform, and improving the absorption effect of the absorption liquid on organic gas in the tail gas;

[0048] 5. When the threaded rod rotates, it can drive the threaded sleeve to move horizontally, and then drive the first magnet and the second magnet to move horizontally. When the second magnet moves to the top of a certain lifting plug, it will suck up the lifting plug, so that the corresponding vertical branch pipe is opened, and the gas can flow out from the vertical branch pipe; when the second magnet moves to other positions, the lifting plug will fall due to its own gravity to block the vertical branch pipe, thereby achieving the purpose of intermittently opening and closing each vertical branch pipe. This intermittent opening and closing design allows only some vertical branch pipes to flow out gas at the same time, which increases the gas pressure of the outflowing gas. The impact force of the air pressure is used to increase the mixing effect between the gas and the absorption liquid, and by constantly changing the outflow position of the gas, the uniformity of the gas concentration absorbed by the absorption liquid is improved, and the absorption effect is further improved. At the same time, the rotation of the threaded rod is related to the rotation of the gas guide tube through a series of gear transmission. When the gas guide tube rotates, the fourth spur gear is stationary, and the third spur gear will rotate when it moves along the fourth spur gear, thereby driving the transmission rod to rotate, and then the second bevel gear is engaged with the first bevel gear to drive the synchronous rotation of multiple threaded rods. This linkage design makes the operation of the entire system more coordinated and efficient, and does not require an additional power source to drive the threaded rod to rotate, which simplifies the system structure and improves the stability and reliability of the system. BRIEF DESCRIPTION OF THE DRAWINGS

[0049] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0050] Figure 1 It is a production process flow chart of the present invention;

[0051] Figure 2 It is a schematic diagram of the production system of the present invention;

[0052] Figure 3 This is a schematic diagram of a triethylamine recovery unit from a first viewing angle of the present invention;

[0053] Figure 4 This is a schematic diagram of the triethylamine recovery unit of the present invention from a second viewing angle;

[0054] Figure 5 It is a three-dimensional diagram of the exhaust gas absorber of the present invention;

[0055] Figure 6 This is an enlarged detail view of the gas distribution mechanism inside the exhaust gas absorber of the present invention from the first perspective;

[0056] Figure 7This is an enlarged detail view of the gas distribution mechanism inside the exhaust gas absorber of the present invention from a second viewing angle;

[0057] Figure 8 This is an enlarged detail view of the gas distribution mechanism inside the exhaust gas absorber of the present invention from a third viewing angle;

[0058] Fig. 9 This is an enlarged detail view of the gas distribution mechanism inside the exhaust gas absorber of the present invention from the fourth viewing angle;

[0059] Fig.10 It is an enlarged detail view of the gas distribution box of the present invention;

[0060] Fig.11 for Fig.10 A zoomed-in detail of position A in the middle;

[0061] In the figure: 1 condensation reaction kettle, 2 concentration reaction kettle, 3 triethylamine recovery kettle, 301 cold and hot medium coil, 302 discharge port, 303 exhaust port, 304 first rotating motor, 305 stirrer, 306 liquid separation observer, 4 reduction kettle, 5 elimination kettle, 6 washing and stratification kettle, 7 thin film evaporator, 8 molecular distiller, 9 condenser, 901 tail gas discharge port, 10 tail gas absorber, 1001 air inlet pipe, 1002 tail gas outlet, 1003 gas guide pipe, 1004 second Rotating motor, 1005 rotating joint, 11 mounting bracket, 1101 threaded rod, 1102 first bevel gear, 1103 transmission rod, 1104 second bevel gear, 1105 third spur gear, 1106 third spur gear, 1107 threaded sleeve, 1108 first magnet, 12 gas distribution box, 1201 vertical branch pipe, 1202 horizontal branch pipe, 1203 first spur gear, 1204 second spur gear, 1205 second magnet, 1206 second magnet. DETAILED DESCRIPTION

[0062] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0063] Example 1

[0064] Reference Figure 1 , a process for producing an erlotinib intermediate, comprising the following steps:

[0065] S1: Condensation reaction

[0066] In the condensation reaction kettle, triethylamine, 2-methylbutynol and purified water are injected in order. 3-bromonitrobenzene and a mixed solution of purified water, cuprous iodide, dichloro-bistriphenylphosphine palladium and triphenylphosphine are added through the manhole, with a loading factor of 70%, and the reaction is kept warm;

[0067] After the reaction is completed, circulating water is passed to cool down and separate the layers, and the upper organic matter is moved to a concentration reactor, and triethylamine is distilled under reduced pressure until no solvent flows out, i.e., M15Z0 concentrated solution;

[0068] The aqueous phase is transferred to a triethylamine recovery kettle, stirred and neutralized by adding 30% liquid alkali, and distilled in layers to remove the triethylamine liquid;

[0069] S1: Reduction reaction

[0070] Put 95% ethanol and drinking water into the reduction kettle, and then put ammonium chloride into the manhole. After starting the stirring, slowly put the iron powder into the reduction kettle from the solid feeder;

[0071] Heat preservation reaction: raise the temperature, slowly add the ethanol solution containing M15Z0 to the reduction kettle, wash the storage tank and pipeline with ethanol after the addition is complete, keep warm, and take samples after the reaction is complete;

[0072] After the reaction is completed, the filtrate is filtered through a filter, the filtrate is concentrated under reduced pressure, the concentrate is evaporated with toluene, and then crystallized and centrifuged to obtain a wet product of M15Z1, and the wet product is dried under reduced pressure to obtain the product M15Z1;

[0073] S3: Elimination reaction

[0074] Put M15Z1 into the elimination kettle in batches, add toluene and potassium hydroxide, stir, control the temperature at 85-90°C, react for 1.5-3 hours, after the reaction is completed, filter press, pass the filtrate into the washing and stratification kettle 6, add drinking water for washing and stratification, drop 30% hydrochloric acid into the oil phase to adjust the pH value of the reaction system, extract and stratify, add dichloromethane into the aqueous phase, drop 30% liquid alkali, stir, confirm that the pH value remains unchanged, dry the organic phase with anhydrous sodium sulfate, filter press with nitrogen to the concentration kettle, control the temperature and reduce the pressure to concentrate to dryness, the concentrate in the kettle is the crude product of 3-aminophenylacetylene M15;

[0075] S4: Refining reaction

[0076] The crude M15 is subjected to thin film distillation and molecular distillation to obtain the finished product M15.

[0077] Example 2

[0078] Reference Figure 2-11, a production system for erlotinib intermediates, comprising a condensation reactor 1, a concentration reactor 2, a triethylamine recovery reactor 3, a condenser 9 and a tail gas absorber 10, a reduction reactor 4, an elimination reactor 5, a washing and layering reactor 6, a thin film evaporator 7 and a molecular distiller 8;

[0079] The exhaust port 303 of the triethylamine recovery kettle 3 is connected to the shell side of the condenser 9, the tail gas discharge port 901 of the condenser 9 is connected to the air inlet pipe 1001 of the tail gas absorber 10, the outside of the triethylamine recovery kettle 3 is provided with a cold and hot medium coil 301, and the top of the tail gas absorber 10 is also provided with a tail gas outlet 1002;

[0080] The waste water after the condensation reaction contains triethylamine, which needs to be recovered. The aqueous phase is first transferred to the triethylamine recovery kettle 3, stirred and 30% liquid alkali is added for neutralization and stratification, and the lower liquid phase is discharged. The organic phase is distilled last time to distill out triethylamine, which is discharged through the exhaust port 303 and condensed and liquefied through the condenser 9 to obtain triethylamine liquid. The non-condensable waste gas flowing out of the tail gas discharge port 901 of the condenser 9 will cause air pollution and needs to be absorbed by the absorption liquid before it can be discharged. The tail gas enters the tail gas absorber 10, and the tail gas absorber 10 is filled with the absorption liquid.

[0081] The triethylamine recovery kettle 3 is provided with an agitator 305 , which is driven to rotate by the first rotating motor 304 . The agitator 305 can improve the mixing effect by stirring, thereby accelerating the neutralization.

[0082] Among them, the bottom end of the triethylamine recovery kettle 3 is provided with a discharge port 302, and a liquid separation observer 306 is installed on the discharge port 302. The liquid separation observer 306 is provided with a transparent observation window. The lower aqueous phase is discharged through the discharge port 302. The liquid state inside the discharge port 302 is observed in real time through the liquid separation observer 306. When the oil phase is found, the valve of the discharge port 302 is immediately closed to prevent the oil phase from being discharged.

[0083] Example 3

[0084] Reference Figure 2-11 The difference between this embodiment and embodiment 2 is that a vertically arranged gas guide pipe 1003 is rotatably installed in the exhaust gas absorber 10, the gas guide pipe 1003 is connected to the intake pipe 1001 through a rotary joint 1005, the gas guide pipe 1003 is driven to rotate by a second rotating motor 1004, and a gas distribution mechanism is provided at the bottom end of the gas guide pipe 1003;

[0085] The exhaust gas enters the exhaust absorber 10 through the intake pipe 1001, and flows into the gas guide pipe 1003 through the rotary joint 1005. Due to the existence of the rotary joint 1005, the second rotating motor 1004 drives the gas guide pipe 1003 to rotate without affecting the connectivity between the two. The exhaust gas is guided to the bottom of the absorption liquid through the gas guide pipe 1003, dispersed and flows out through the gas distribution mechanism, and fully contacts with the absorption liquid, thereby absorbing the organic gas in the exhaust gas.

[0086] Example 4

[0087] Reference Figure 2-11 The difference between this embodiment and embodiment 3 is that the gas distribution mechanism includes a plurality of mounting brackets 11, a gas distribution box 12 is fixed to the top of the mounting bracket 11, the gas distribution box 12 is connected to the gas guide pipe 1003 through a connecting pipe 13, a plurality of vertical branch pipes 1201 are rotatably mounted on the top of the gas guide pipe 1003, a plurality of horizontal branch pipes 1202 are fixed to the outside of the vertical branch pipes 1201, and a gas outlet is opened on the horizontal branch pipes 1202;

[0088] When the gas guide pipe 1003 rotates, it can drive the gas distribution box 12 to rotate accordingly, so that the positions of the vertical branch pipe 1201 and the horizontal branch pipe 1202 can be continuously changed during the exhaust process to further improve the gas distribution effect.

[0089] Among them, a first spur gear 1203 is fixed on the outside of the vertical branch pipe 1201, and a second spur gear 1204 is rotatably installed between adjacent first spur gears 1203 on the gas distribution box 12, and the first spur gear 1203 and the second spur gear 1204 are meshed in sequence, and a gear ring 14 is fixed on the inner wall of the top end of the exhaust gas absorber 10 through a bracket, and the first spur gear 1203 closest to the gas guide pipe 1003 is meshed with the gear ring 14;

[0090] When the gas guide tube 1003 rotates, since the gear ring 14 is stationary, one of the first spur gears 1203 will rotate while moving around the gear ring 14, and then through the transmission of the second spur gear 1204, it drives multiple first spur gears 1203 to rotate synchronously, and then drives multiple vertical branch pipes 1201 to rotate synchronously, which further improves the gas distribution effect and can also drive the horizontal branch pipes 1202 to stir the absorption liquid, thereby improving the uniformity of the absorption liquid and improving the absorption effect.

[0091] Example 5

[0092] Reference Figure 2-11The difference between this embodiment and embodiment 4 is that a threaded rod 1101 is rotatably installed on one side of the mounting bracket 11 away from the gas distribution box 12, a threaded sleeve 1107 is installed on the external thread of the threaded rod 1101, the threaded sleeve 1107 is horizontally movably installed on the mounting bracket 11 through a guide mechanism, and a first magnet 1108 is fixed on the threaded sleeve 1107, the first magnet 1108 is in movably contact with the surface of the gas distribution box 12, and a second magnet 1205 is movably installed on the inner wall of the gas distribution box 12 through a guide rail, the first magnet 1108 and the second magnet 1205 attract each other, and a lifting plug 1206 is movably installed in the gas distribution box 12, the lifting plug 1206 is made of magnetic metal, and the lifting plug 1206 corresponds to the vertical branch pipe 1201;

[0093] When the threaded rod 1101 rotates, it can drive the threaded sleeve 1107 to move horizontally, and then drive the first magnet 1108 and the second magnet 1205 to move horizontally. When the second magnet 1205 moves to the top of a certain lifting plug 1206, it will suck up the lifting plug 1206, so that the corresponding vertical branch pipe 1201 is opened, and the gas can flow out of the vertical branch pipe 1201. Only when the lifting plug 1206 is sucked up, can the gas flow out of the corresponding vertical branch pipe 1201. When the magnet 1205 moves to other positions, the lifting plug 1206 will fall due to its own gravity and block the vertical branch pipes 1201, thereby achieving the purpose of intermittently opening and closing each vertical branch pipe 1201, so that only part of the vertical branch pipes 1201 can flow out gas at the same time, thereby increasing the gas pressure of the outflowing gas, and increasing the mixing effect between the gas and the absorption liquid through the impact force of the gas pressure. By constantly changing the gas outflow position, the uniformity of the gas concentration absorbed by the absorption liquid is improved, thereby improving the absorption effect.

[0094] Among them, a first bevel gear 1102 is fixed to one end of the threaded rod 1101, and a vertically arranged transmission rod 1103 is rotatably installed on the mounting bracket 11, one end of the transmission rod 1103 is fixed to the second bevel gear 1104, the second bevel gear 1104 is meshed with the first bevel gear 1102, and a third spur gear 1105 is fixed to the other end of the transmission rod 1103, and a fourth spur gear 1106 is fixed to the inner wall of the bottom end of the exhaust absorber 10, and the fourth spur gear 1106 is meshed with the third spur gear 1105. When the gas guide pipe 1003 rotates, the fourth spur gear 1106 is stationary, and the third spur gear 1105 will rotate when walking along the fourth spur gear 1106, thereby driving the transmission rod 1103 to rotate, and then through the meshing of the second bevel gear 1104 with the first bevel gear 1102, the multiple threaded rods 1101 can be driven to rotate synchronously.

[0095] In the description of the present invention, it should be understood that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", "clockwise", "counterclockwise", "axial", "radial", "circumferential" and the like indicate orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the referred device or element must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as limiting the present invention.

[0096] In the present invention, unless otherwise clearly specified and limited, the terms "set", "install", "connect", "connect", "fix" and the like should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral one; it can be a mechanical connection, a direct connection, or an indirect connection through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0097] The control method of the present invention is automatic control through a controller. The control circuit of the controller can be implemented by simple programming by technicians in this field. The provision of power is also common knowledge in this field. The present invention is mainly used to protect mechanical devices, so the present invention will no longer explain the control method and circuit connection in detail.

[0098] The above description is only a preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical scheme and inventive concept of the present invention within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.

Claims

1. A process for producing an erlotinib intermediate, characterized in that: The following steps are involved: S1: Condensation reaction Into the condensation reaction kettle (1), triethylamine, 2-methylbutynol, and purified water are introduced in order. 3-bromonitrobenzene and a mixed solution containing (purified water, cuprous iodide, dichloro-bis(triphenylphosphine)palladium, and triphenylphosphine) are introduced through the manhole; After the reaction is completed, circulating water is passed to cool down and separate the layers. The upper organic matter is transferred to the concentration reactor (2), and triethylamine is distilled under reduced pressure until no solvent flows out, i.e., M15Z0 concentrated solution. The aqueous phase is transferred to a triethylamine recovery kettle (3), stirred and neutralized by adding 30% liquid alkali, and distilled in layers to remove the triethylamine liquid; S1: Reduction reaction Put 95% ethanol and drinking water into the reduction kettle (4), and then put ammonium chloride into the manhole. After starting the stirring, slowly put the iron powder into the reduction kettle (4) from the solid feeder; Insulation reaction: Raise the temperature, slowly add the ethanol solution containing M15Z0 to the reduction kettle (4), wash the storage tank and pipeline with ethanol after the addition is complete, keep warm, and take samples after the reaction is complete; After the reaction is completed, the filtrate is filtered through a filter, the filtrate is concentrated under reduced pressure, the concentrate is evaporated with toluene, and then crystallized and centrifuged to obtain a wet product of M15Z1, and the wet product is dried under reduced pressure to obtain the product M15Z1; S3: Elimination reaction M15Z1 is put into the elimination kettle (5) in batches, and toluene and potassium hydroxide are added and stirred. After the reaction is completed, the filtrate is passed into the washing and layering kettle (6) after pressure filtration, and drinking water is added to wash and layer. 30% hydrochloric acid is added dropwise to the oil phase to adjust the pH value of the reaction system, and extraction and layering are performed. Dichloromethane is added to the aqueous phase, and 30% liquid alkali is added dropwise, and stirred to confirm that the pH value remains unchanged. The organic phase is dried with anhydrous sodium sulfate, and filtered by nitrogen pressure to the concentration kettle, and the temperature is controlled and reduced pressure is concentrated to dryness. The concentrated liquid in the kettle is 3-aminophenylacetylene (M15 crude product); S4: Refining reaction The crude M15 is subjected to thin film distillation and molecular distillation to obtain the finished product M15.

2. A production system for an erlotinib intermediate, applied to a process for producing an erlotinib intermediate as claimed in claim 1, characterized in that: It comprises a condensation reaction kettle (1), a concentration reaction kettle (2), a triethylamine recovery kettle (3), a condenser (9), a tail gas absorber (10), a reduction kettle (4), an elimination kettle (5), a washing and stratification kettle (6), a thin film evaporator (7) and a molecular distiller (8); The exhaust port (303) of the triethylamine recovery kettle (3) is communicated with the shell side of the condenser (9), the tail gas discharge port (901) of the condenser (9) is communicated with the air inlet pipe (1001) of the tail gas absorber (10), a cold and hot medium coil (301) is arranged outside the triethylamine recovery kettle (3), and a tail gas outlet (1002) is also arranged at the top of the tail gas absorber (10).

3. A system for producing an erlotinib intermediate according to claim 2, characterized in that: The triethylamine recovery kettle (3) is provided with an agitator (305), and the agitator (305) is driven to rotate by a first rotating motor (304).

4. A production system for producing an erlotinib intermediate according to claim 2, characterized in that: The bottom end of the triethylamine recovery kettle (3) is provided with a discharge port (302), a liquid separation observer (306) is installed on the discharge port (302), and a transparent observation window is provided on the liquid separation observer (306).

5. A production system for producing an erlotinib intermediate according to claim 2, characterized in that: A vertically arranged gas guide pipe (1003) is rotatably installed in the exhaust gas absorber (10); the gas guide pipe (1003) is connected to the intake pipe (1001) via a rotary joint (1005); the gas guide pipe (1003) is driven to rotate by a second rotating motor (1004); and a gas distribution mechanism is provided at the bottom end of the gas guide pipe (1003).

6. A production system for producing an erlotinib intermediate according to claim 5, characterized in that: The gas distribution mechanism comprises a plurality of mounting brackets (11), a gas distribution box (12) being fixed at the top of the mounting brackets (11), the gas distribution box (12) being connected to the gas guide pipe (1003) via a connecting pipe (13), a plurality of vertical branch pipes (1201) being rotatably mounted at the top of the gas guide pipe (1003), a plurality of horizontal branch pipes (1202) being fixed outside the vertical branch pipes (1201), and a gas outlet being provided on the horizontal branch pipes (1202).

7. A production system for producing an erlotinib intermediate according to claim 6, characterized in that: A first spur gear (1203) is fixed to the outside of the vertical branch pipe (1201), and a second spur gear (1204) is rotatably installed between adjacent first spur gears (1203) on the gas distribution box (12), and the first spur gear (1203) and the second spur gear (1204) are meshed in sequence. A gear ring (14) is fixed to the inner wall of the top end of the exhaust gas absorber (10) through a bracket, and the first spur gear (1203) closest to the gas guide pipe (1003) is meshed with the gear ring (14).

8. A production system for producing an erlotinib intermediate according to claim 7, characterized in that: A threaded rod (1101) is rotatably mounted on one side of the mounting bracket (11) away from the gas distribution box (12); a threaded sleeve (1107) is mounted on the external thread of the threaded rod (1101); the threaded sleeve (1107) is horizontally movably mounted on the mounting bracket (11) via a guide mechanism; a first magnet (1108) is fixed on the threaded sleeve (1107); the first magnet (1108) is in movably contact with the surface of the gas distribution box (12); a second magnet (1205) is movably mounted on the inner wall of the gas distribution box (12) via a guide rail; the first magnet (1108) and the second magnet (1205) attract each other; a lifting plug (1206) is movably mounted in the gas distribution box (12); the lifting plug (1206) is made of magnetic metal; and the lifting plug (1206) corresponds to the vertical branch pipe (1201).

9. A production system for producing an erlotinib intermediate according to claim 8, characterized in that: A first bevel gear (1102) is fixed to one end of the threaded rod (1101), a vertically arranged transmission rod (1103) is rotatably mounted on the mounting bracket (11), one end of the transmission rod (1103) is fixed to a second bevel gear (1104), and the second bevel gear (1104) is meshed with the first bevel gear (1102).

10. A production system for producing an erlotinib intermediate according to claim 9, characterized in that: A third spur gear (1105) is fixed to the other end of the transmission rod (1103), a fourth spur gear (1106) is fixed to the inner wall of the bottom end of the exhaust gas absorber (10), and the fourth spur gear (1106) is meshed with the third spur gear (1105).

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