CN110950885B - Method and device for continuously preparing prasugrel intermediate through countercurrent extraction - Google Patents
Method and device for continuously preparing prasugrel intermediate through countercurrent extraction Download PDFInfo
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- CN110950885B CN110950885B CN201911242832.3A CN201911242832A CN110950885B CN 110950885 B CN110950885 B CN 110950885B CN 201911242832 A CN201911242832 A CN 201911242832A CN 110950885 B CN110950885 B CN 110950885B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
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- B01D3/00—Distillation or related exchange processes in which liquids are contacted with gaseous media, e.g. stripping
- B01D3/009—Distillation or related exchange processes in which liquids are contacted with gaseous media, e.g. stripping in combination with chemical reactions
Abstract
The invention relates to the field of medicines, and particularly discloses a method for continuously and efficiently preparing prasugrel. Mixing the compounds according to a molar ratio
A compound of
And pumping the dichloromethane solution of triethylamine into a reaction kettle, heating to the reaction temperature, and reacting for a certain time. Pumping the material liquid in the reaction kettle into the top of the turntable tower at a certain flow rate, pumping purified water from the bottom of the turntable tower for countercurrent extraction, and adjusting the rotation speed of the turntable in the turntable tower to fully mix the two phases. And the raffinate water phase is discharged from the top of the tower, and the raffinate dichloromethane phase is discharged from the bottom of the tower. And concentrating the dichloromethane phase under reduced pressure, cooling, crystallizing and filtering to obtain the intermediate of the prasugrel. According to the invention, through a countercurrent extraction method, triethylamine hydrobromide generated in the reaction process can be synchronously and effectively removed, the problems of difficult stirring and the like caused by precipitation in a dichloromethane system are avoided, and the conversion rate of the reaction and the yield of the prasugrel intermediate are effectively improved by the application of the method.
Description
Technical Field
The invention relates to the field of medicines, and particularly relates to a method for continuously producing a prasugrel intermediate 5- (2-cyclopropyl-1- (2-fluorophenyl) -2-oxyethyl) -5,6,7 by countercurrent extractiona-tetrahydrothieno [3,2-c]-2(4H) -a process for pyridone and a plant therefore.
Background
Prasugrel is an oral antiplatelet drug developed by american gifts and japan first pharmaceutical three co-ltd, and its hydrochloride for clinical use is marketed in the united states under the trade name efint by FDA approval in 7 months in 2009. Prasugrel is a prodrug whose pharmacological action is to inhibit platelet activation and aggregation by irreversible binding of active metabolites to platelet adenosine diphosphate receptors. The clinical application is mainly to prevent atherosclerotic thrombotic events in patients with acute coronary syndrome who have received an emergency and will undergo a delayed percutaneous coronary intervention. Compared with the similar medicament clopidogrel on the market, the clopidogrel has faster, stronger and more durable effect of inhibiting platelet aggregation and has very wide market prospect.
5- (2-cyclopropyl-1- (2-fluorophenyl) -2-oxyethyl) -5,6,7a-tetrahydrothieno [3,2-c]-2(4H) Pyridones (compound III) are very important key intermediates for the synthesis of prasugrel. The main synthesis process at present is 5,6,7a-tetrahydrothieno [3,2-c]-2(4H) -pyridone (compound I) and 2-bromo-1-cyclopropyl-2- (2-fluorophenyl) -1-ethanone (compound II) as starting materials. However, hydrogen bromide produced in the reaction and an acid-binding agent triethylamine generate triethylamine hydrobromide, the solubility of the triethylamine hydrobromide in a dichloromethane system is extremely low, and the triethylamine hydrobromide is precipitated in a solid form, so that a reaction solution is viscous, and a large amount of the reaction solution cannot be stirred after being precipitated, which causes great difficulty in industrial scale-up production. How to effectively remove the triethylamine hydrobromide is a key to the scalability of the prasugrel production process.
Disclosure of Invention
A method for continuously preparing prasugrel intermediate by countercurrent extraction comprises the following operation steps:
s1, pumping dichloromethane solution of a compound I, a compound II and triethylamine into a reaction kettle, and heating;
s2, pumping the material liquid in the reaction kettle into the top of the rotating disc tower, pumping purified water from the bottom of the rotating disc tower for countercurrent extraction, and adjusting the rotating speed of a rotating disc in the rotating disc tower to fully mix the two phases;
s3, discharging the extracted water phase from the top of the rotating disc tower, discharging the extracted dichloromethane phase from the bottom of the rotating disc tower, decompressing and concentrating the dichloromethane phase, cooling and crystallizing, and filtering to obtain the intermediate of the prasugrel; the compound I is 5,6,7a-tetrahydrothieno [3,2-c]-2(4H) -a pyridone; the compound II is 2-bromo-1-cyclopropyl-2- (2-fluorophenyl) -1-ethanone. Triethylamine reacts with cyanogen bromide to generate triethylamine hydrobromide which is easy to dissolve in water and difficult to dissolve in dichloromethane, so that when the triethylamine hydrobromide appears in reaction liquid, the viscosity of the reaction liquid is improved, the reaction liquid can not be stirred in a reactor, on one hand, the utilization rate of other reactants is reduced, and the yield of the prasugrel intermediate is reduced; on the other hand, the difficulty of purifying the prasugrel intermediate is improved. In the invention, a turntable tower countercurrent extraction mode is adopted, the triethylamine hydrobromide is dissolved by water, and the prasugrel intermediate is insoluble in water, so that the triethylamine hydrobromide is removed by extraction and liquid separation; the countercurrent extraction can increase the contact area of the water phase and the dichloromethane phase by utilizing the gravity of the dichloromethane phase, thereby improving the efficiency of extraction and liquid separation.
Further, the dichloromethane phase after cooling and crystal precipitation is sent back to the reactor to participate in the reaction again. All prasugrel intermediates in the dichloromethane phase cannot be precipitated and collected in the cooling crystallization process, so that the dichloromethane phase is sent back to the reactor, on one hand, the dichloromethane can be recycled, and on the other hand, the waste of the prasugrel intermediate can be reduced.
Further, in S3, the raffinate dichloromethane phase is discharged from the bottom of the rotating disc tower and sent into an evaporation kettle for reduced pressure concentration, the obtained dichloromethane distillate is discharged from the top of the evaporation kettle, the bottom liquid of the evaporation kettle is sent into a cooling crystallizer for cooling crystallization and then sent into a continuous filtration centrifuge for filtration to obtain a prasugrel intermediate (compound III), and the reflux filtrate obtained after centrifugation is sent back into the reactor for continuous reaction.
Further, the method for continuously preparing the prasugrel intermediate through countercurrent extraction has the molar ratio of the compound I to the compound II being 1: 1-1: 4.
Further, a process for the continuous preparation of prasugrel intermediates by countercurrent extraction, compounds
And the molar ratio of triethylamine to the organic solvent is 1: 1-1: 8. The excessive triethylamine can ensure the complete reaction of the compound I and improve the reactionUtilization ratio of the reagent.
Further, the method for continuously preparing the prasugrel intermediate through countercurrent extraction has the reaction temperature of 10-40 ℃.
Further, the method for continuously preparing the prasugrel intermediate through countercurrent extraction has the reaction time of 1-10 hours.
Further, the method for continuously preparing the prasugrel intermediate through countercurrent extraction has the advantage that the flow of a reaction liquid pumped into a rotating disc tower is 0.10-0.98 times of the flow of a reactant mixture liquid continuously added.
Further, in the method for continuously preparing the prasugrel intermediate through countercurrent extraction, the flow of the reaction liquid pumped into the rotating disc tower is 0.1-10 times of the flow of the purified water pumped into the tower bottom.
Further, the method for continuously preparing the prasugrel intermediate through countercurrent extraction has the rotating speed of a rotating disc tower of 30-240 rpm.
Further, a method for continuously preparing prasugrel intermediate by countercurrent extraction,
as a preferred scheme, the device for continuously preparing the prasugrel intermediate through countercurrent extraction comprises a reaction kettle, a turntable tower, an evaporation kettle, a cooling crystallizer and a continuous filtering centrifuge which are sequentially connected, wherein the bottom of the reaction kettle is connected with the top of the turntable tower, the bottom of the turntable tower is connected with the top of the evaporation kettle, the evaporation kettle is used for carrying out reduced pressure concentration on the bottom discharge material of the turntable tower to form a dichloromethane phase, and the bottom of the evaporation kettle is connected with the cooling crystallizer and is used for cooling and recrystallizing the dichloromethane phase after the reduced pressure concentration; and the continuous filtering centrifuge is connected with the top of the cooling crystallizer and is used for centrifugally separating the obtained crystals and solution.
Further, the rotating disc tower is provided with a heat preservation water bath inlet and a heat preservation water bath outlet, and water bath heating is carried out on the rotating disc tower, wherein the water bath temperature is 40-50 ℃. The water bath heat preservation can improve the solubility of the triethylamine hydrobromide in water, thereby improving the countercurrent extraction efficiency and improving the product yield.
Further, the bottom of the continuous filtration centrifuge is connected with the top of the reactor and is used for returning the dichloromethane phase obtained after centrifugation to the reactor.
In conclusion, the invention has the following beneficial effects:
according to the method, triethylamine hydrobromide which is generated by the reaction of triethylamine serving as an acid-binding agent and cyanogen bromide and is insoluble in a dichloromethane system is dissolved in water in a countercurrent extraction mode and discharged from a rotating disc tower, so that the viscosity of a reaction liquid is reduced, the industrial continuous production of the prasugrel intermediate is realized, and the purification method of the prasugrel intermediate and the yield of the prasugrel intermediate are simplified.
Drawings
FIG. 1 is a schematic view of the apparatus of the present invention;
FIG. 2 is a molecular structural formula of compound I in the present invention;
FIG. 3 is a molecular structural formula of compound II in the present invention;
FIG. 4 is a molecular structural formula of compound III in the present invention;
FIG. 5 shows the reaction equation of the present invention.
The symbols in the figure are 1-reaction vessel, 2-rotating disc tower, 3-evaporation vessel, 4-cooling crystallizer, 5-continuous filtration centrifuge.
Detailed Description
The present invention will be described in further detail with reference to the accompanying drawings.
In which like parts are designated by like reference numerals. It should be noted that the terms "front," "back," "left," "right," "upper" and "lower" used in the following description refer to directions in the drawings, and the terms "bottom" and "top," "inner" and "outer" refer to directions toward and away from, respectively, the geometric center of a particular component.
The HPLC detection method of prasugrel related by the invention comprises the following steps:
a chromatographic column: kromasil C18 column (250 mm. times.4.6 mm. times.5 μm);
mobile phase: acetonitrile-water (90: 10);
column temperature: 30 ℃;
flow rate: 1 ml/min;
sample introduction amount: 20 mu l of the mixture;
UV detection wavelength: 220 nm.
A method for continuously preparing prasugrel intermediate by countercurrent extraction comprises the following operation steps:
s1, pumping dichloromethane solution of a compound I, a compound II and triethylamine into a reaction kettle, and heating;
s2, pumping the material liquid in the reaction kettle into the top of the rotating disc tower, pumping purified water from the bottom of the rotating disc tower for countercurrent extraction, and adjusting the rotating speed of a rotating disc in the rotating disc tower to fully mix the two phases;
s3, discharging the extracted water phase from the top of the rotating disc tower, discharging the extracted dichloromethane phase from the bottom of the rotating disc tower, decompressing and concentrating the dichloromethane phase, cooling and crystallizing, and filtering to obtain the intermediate of the prasugrel; the compound I is 5,6,7a-tetrahydrothieno [3,2-c]-2(4H) -a pyridone; the compound II is 2-bromo-1-cyclopropyl-2- (2-fluorophenyl) -1-ethanone, wherein the molar ratio of the compound I to the compound II is 1: 1-1: 4, the molar ratio of the compound I to triethylamine is 1: 1-1: 8, the reaction temperature is 10-40 ℃, the reaction time is 1-10 hours, the flow rate of a reaction liquid pumped into the rotating disc tower is 0.10-0.98 times of the flow rate of a mixture liquid in which the reactants are continuously added, the flow rate of the reaction liquid pumped into the rotating disc tower is 0.1-10 times of the flow rate of purified water pumped into the tower bottom, and the rotating disc rotating speed of the rotating disc tower is 30-240 rpm.
A device for continuously preparing a prasugrel intermediate through countercurrent extraction comprises a reaction kettle 1, a turntable tower 2, an evaporation kettle 3, a cooling crystallizer 4 and a continuous filtering centrifuge 5 which are sequentially connected, wherein the bottom of the reaction kettle 1 is connected with the top of the turntable tower 2, the bottom of the turntable tower 2 is connected with the top of the evaporation kettle 3, the evaporation kettle 3 is used for carrying out reduced pressure concentration on the bottom discharge of the turntable tower 2 to form a dichloromethane phase, and the bottom of the evaporation kettle 3 is connected with the cooling crystallizer 4 and is used for carrying out cooling recrystallization on the dichloromethane phase after the reduced pressure concentration; a continuous filtration centrifuge 5 is connected to the top of the cooling crystallizer 4 for centrifuging the crystals and the solution obtained.
Example 1: a method for continuously preparing prasugrel intermediate by countercurrent extraction and a device thereof are disclosed, as shown in figure 1:
s1, pumping a dichloromethane mixed solution with a molar ratio of a compound I to a compound II of 1:1 and a molar ratio of the compound I to triethylamine of 1:8 into a reaction kettle 1 at a flow rate of 10L/h, heating to 30 ℃, and reacting for 6 h;
s2, pumping the feed liquid in the reaction kettle 1 into the top of the rotating disc tower 2 at a flow rate of 4L/h, pumping purified water from the bottom of the rotating disc tower 2 at a flow rate of 8L/h, and adjusting the rotating speed of a rotating disc in the rotating disc tower 2 to 240rpm for countercurrent extraction;
s3, discharging extracted water phase from the top of the rotating disc tower 2, discharging extracted dichloromethane phase from the bottom of the rotating disc tower 2, feeding the extracted dichloromethane phase into an evaporation kettle 3 for reduced pressure concentration, discharging obtained dichloromethane distillate from the top of an evaporation kettle 3, feeding kettle bottom liquid of the evaporation kettle 3 into a cooling crystallizer 4 for cooling crystallization, feeding the obtained product into a continuous filtration centrifuge 5 for filtration to obtain a prasugrel intermediate (compound III), feeding the obtained reflux filtrate obtained after centrifugation back into the reactor 1 for continuous reaction, and calculating the yield of the prasugrel intermediate to be 89.2% after drying a filter cake.
Example 2: a method for continuously preparing prasugrel intermediate by countercurrent extraction and a device thereof are disclosed, as shown in figure 1:
s1, mixing the compound
And compounds
At a molar ratio of 1:1.5, compound
Pumping a dichloromethane mixed solution with a triethylamine molar ratio of 1:1 into a reaction kettle 1 at a flow rate of 10L/h, heating to 40 ℃, and reacting for 8 h;
s2, pumping the feed liquid in the reaction kettle 1 into the top of the rotary disc tower 2 at a flow rate of 6L/h, pumping purified water into the bottom of the rotary disc tower 2 at a flow rate of 6L/h, and adjusting the rotating speed of a rotary disc in the rotary disc tower 2 to perform countercurrent extraction at 180rpm
S3, discharging the extracted water phase from the top of the rotating disc tower 2, and discharging the extracted dichloromethane phase from the bottom of the rotating disc tower 2; and (3) discharging the extracted dichloromethane phase from the bottom of the rotating disc tower 2, feeding the extracted dichloromethane phase into an evaporation kettle 3 for reduced pressure concentration, discharging the obtained dichloromethane distillate from the top of the evaporation kettle 3, feeding the bottom liquid of the evaporation kettle 3 into a cooling crystallizer 4 for cooling crystallization, feeding the obtained product into a continuous filtration centrifuge 5 for filtration to obtain a prasugrel intermediate (compound III), feeding the obtained reflux filtrate obtained after centrifugation back into the reactor 1 for continuous reaction, and drying the filter cake of the prasugrel intermediate to obtain the yield of 87.5%.
Example 3: a method for continuously preparing prasugrel intermediate by countercurrent extraction and a device thereof are disclosed, as shown in figure 1:
s1, mixing the compound
And compounds
At a molar ratio of 1:2, compound
Pumping a dichloromethane mixed solution with a triethylamine molar ratio of 1:2.5 into a reaction kettle 1 at a flow rate of 10L/h, heating to 10 ℃, and reacting for 10 h;
s2, pumping the feed liquid in the reaction kettle 1 into the top of the rotary disc tower 2 at a flow rate of 8L/h, pumping purified water into the bottom of the rotary disc tower 2 at a flow rate of 2.67L/h, and adjusting the rotating speed of a rotary disc in the rotary disc tower 2 to 120rpm for countercurrent extraction;
s3, discharging extracted water phase from the top of the rotating disc tower 2, discharging extracted dichloromethane phase from the bottom of the rotating disc tower 2, feeding the extracted dichloromethane phase into an evaporation kettle 3 for reduced pressure concentration, discharging obtained dichloromethane distillate from the top of an evaporation kettle 3, feeding bottom liquid of the evaporation kettle 3 into a cooling crystallizer 4 for cooling crystallization, feeding the obtained product into a continuous filtration centrifuge 5 for filtration to obtain a prasugrel intermediate (compound III), feeding the obtained reflux filtrate obtained after centrifugation back into the reactor 1 for continuous reaction, and calculating the yield of the prasugrel intermediate to be 86.1% after drying filter cakes.
Example 4: a method for continuously preparing prasugrel intermediate by countercurrent extraction and a device thereof are disclosed, as shown in figure 1:
s1, mixing the compound
And compounds
The molar ratio is 1:2.5, the compound
Pumping a dichloromethane mixed solution with a triethylamine molar ratio of 1:4 into a reaction kettle 1 at a flow rate of 10L/h, heating to 15 ℃, and reacting for 1 h;
s2, pumping the feed liquid in the reaction kettle 1 into the top of the rotary disc tower 2 at a flow rate of 9.8L/h, simultaneously pumping purified water into the bottom of the rotary disc tower 2 at a flow rate of 1.96L/h, and adjusting the rotating speed of a rotary disc in the rotary disc tower 2 to 90rpm for countercurrent extraction
S3, discharging extracted water phase from the top of the rotating disc tower 2, discharging extracted dichloromethane phase from the bottom of the rotating disc tower 2, feeding the extracted dichloromethane phase into an evaporation kettle 3 for reduced pressure concentration, discharging obtained dichloromethane distillate from the top of the evaporation kettle 3, feeding bottom liquid of the evaporation kettle 3 into a cooling crystallizer 4 for cooling crystallization, feeding the obtained product into a continuous filtration centrifuge 5 for filtration to obtain a prasugrel intermediate (compound III), feeding the obtained reflux filtrate obtained after centrifugation back into the reactor 1 for continuous reaction, and calculating the yield of the prasugrel intermediate filter cake to be 90.7% after drying.
Wherein the rotating disc tower 2 is provided with a heat-preservation water bath inlet 5 and a heat-preservation water bath outlet 6, the rotating disc tower 2 is heated in a water bath, the temperature of the water bath is 40 ℃, the solubility of the triethylamine hydrobromide in the water is improved, the countercurrent extraction efficiency is improved, and the product yield is improved.
Example 5: a method for continuously preparing prasugrel intermediate by countercurrent extraction and a device thereof are disclosed, as shown in figure 1:
s1, mixing the compound
And compounds
The molar ratio is 1:3, compounds
Pumping a dichloromethane mixed solution with a triethylamine molar ratio of 1:6 into a reaction kettle 1 at a flow rate of 10L/h, heating to 20 ℃, and reacting for 2.5 h;
s2, pumping the feed liquid in the reaction kettle 1 into the top of the rotating disc tower 2 at a flow rate of 1L/h, simultaneously pumping purified water into the bottom of the rotating disc tower 2 at a flow rate of 0.1L/h, and adjusting the rotating speed of a rotating disc in the rotating disc tower 2 to 60rpm for countercurrent extraction;
s3, discharging extracted water phase from the top of the rotating disc tower 2, discharging extracted dichloromethane phase from the bottom of the rotating disc tower 2, feeding the extracted dichloromethane phase into an evaporation kettle 3 for reduced pressure concentration, discharging obtained dichloromethane distillate from the top of the evaporation kettle 3, feeding bottom liquid of the evaporation kettle 3 into a cooling crystallizer 4 for cooling crystallization, feeding the obtained product into a continuous filtration centrifuge 5 for filtration to obtain a prasugrel intermediate (compound III), feeding the obtained reflux filtrate obtained after centrifugation back into the reactor 1 for continuous reaction, and calculating the yield of the prasugrel intermediate filter cake to be 84.9% after drying.
Example 6: a method for continuously preparing prasugrel intermediate by countercurrent extraction and a device thereof are disclosed, as shown in figure 1:
s1, mixing the compound
And compounds
At a molar ratio of 1:4, compound
Pumping a dichloromethane mixed solution with a triethylamine molar ratio of 1:7 into a reaction kettle 1 at a flow rate of 10L/h, heating to 25 ℃, and reacting for 4 h;
s2, pumping the feed liquid in the reaction kettle 1 into the top of the rotary disc tower 2 at a flow rate of 2L/h, pumping purified water into the bottom of the rotary disc tower 2 at a flow rate of 20L/h, and adjusting the rotating speed of a rotary disc in the rotary disc tower 2 to 30rpm for countercurrent extraction
S3, discharging extracted water phase from the top of the rotating disc tower 2, discharging extracted dichloromethane phase from the bottom of the rotating disc tower 2, feeding the extracted dichloromethane phase into an evaporation kettle 3 for reduced pressure concentration, discharging obtained dichloromethane distillate from the top of the evaporation kettle 3, feeding bottom liquid of the evaporation kettle 3 into a cooling crystallizer 4 for cooling crystallization, feeding the obtained product into a continuous filtration centrifuge 5 for filtration to obtain a prasugrel intermediate (compound III), feeding the obtained reflux filtrate obtained after centrifugation back into the reactor 1 for continuous reaction, and calculating the yield of the prasugrel intermediate filter cake to be 88.7 percent after drying.
The present embodiment is only for explaining the present invention, and it is not limited to the present invention, and those skilled in the art can make modifications of the present embodiment without inventive contribution as needed after reading the present specification, but all of them are protected by patent law within the scope of the claims of the present invention.
Claims (5)
1. A method for continuously preparing prasugrel intermediate by countercurrent extraction is characterized by comprising the following operation steps:
s1, pumping dichloromethane solution of a compound I, a compound II and triethylamine into a reaction kettle, and heating;
s2, pumping the material liquid in the reaction kettle into the top of the rotating disc tower, pumping purified water from the bottom of the rotating disc tower for countercurrent extraction, and adjusting the rotating speed of a rotating disc in the rotating disc tower to fully mix the two phases;
s3, discharging the extracted water phase from the top of the rotating disc tower, discharging the extracted dichloromethane phase from the bottom of the rotating disc tower, concentrating the dichloromethane phase under reduced pressure, cooling for crystallization, and filtering to obtain the prasugrel intermediate 5- (2-cyclopropyl-1- (2-fluorophenyl) -2-oxyethyl) -5,6,7a-tetrahydrothieno [3,2-c]-2(4H) -a pyridone; the compound I is 5,6,7a-tetrahydrothieno [3,2-c]-2(4H) -a pyridone; the compound II is 2-bromo-1-cyclopropyl-2- (2-fluorophenyl) -1-ethanone; the reaction temperature is 10-40 ℃; the reaction time is 1-10 h; the flow of the reactant liquid pumped into the rotating disc tower is 0.10-0.98 times of the flow of the reactant mixed liquid continuously added; the flow of the reaction liquid pumped into the rotating disc tower is 0.1-10 times of the flow of the purified water pumped into the tower bottom; the rotating speed of a rotating disc of the rotating disc tower is 30-240 rpm.
2. The method for continuously preparing the prasugrel intermediate through countercurrent extraction as claimed in claim 1, wherein the molar ratio of the compound I to the compound II is 1: 1-1: 4.
3. The method for continuously preparing the prasugrel intermediate through countercurrent extraction as claimed in claim 1, wherein the molar ratio of the compound I to triethylamine is 1: 1-1: 8.
4. The method for continuously preparing the prasugrel intermediate through countercurrent extraction according to claim 1, wherein the molar ratio of the compound I to the compound II is 1: 1-1: 4, the molar ratio of the compound I to triethylamine is 1: 1-1: 8, the reaction temperature is 10-40 ℃, the reaction time is 1-10 h, the flow rate of the reaction liquid pumped into the rotating disc tower is 0.10-0.98 times of the flow rate of the continuously added reactant mixed liquid, the flow rate of the reaction liquid pumped into the rotating disc tower is 0.1-10 times of the flow rate of the purified water pumped into the tower bottom, and the rotating disc rotating speed of the rotating disc tower is 30-240 rpm.
5. The device for continuously preparing the prasugrel intermediate through countercurrent extraction according to claim 1, which is characterized by comprising a reaction kettle (1), a rotating disc tower (2), an evaporation kettle (3), a cooling crystallizer (4) and a continuous filtering centrifuge (5) which are sequentially connected, wherein the bottom of the reaction kettle (1) is connected with the top of the rotating disc tower (2), the bottom of the rotating disc tower (2) is connected with the top of the evaporation kettle (3), the evaporation kettle (3) is used for carrying out reduced pressure concentration on the bottom discharge of the rotating disc tower (2) to form a dichloromethane phase, and the bottom of the evaporation kettle (3) is connected with the cooling crystallizer (4) and is used for carrying out cooling recrystallization on the dichloromethane phase after the reduced pressure concentration; the continuous filtering centrifuge (5) is connected with the top of the cooling crystallizer (4) and is used for centrifugally separating the obtained crystals and solution.
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