CN112221451A - Low-temperature reaction device for preparing sitagliptin phosphate intermediate - Google Patents

Low-temperature reaction device for preparing sitagliptin phosphate intermediate Download PDF

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Publication number
CN112221451A
CN112221451A CN202011115232.3A CN202011115232A CN112221451A CN 112221451 A CN112221451 A CN 112221451A CN 202011115232 A CN202011115232 A CN 202011115232A CN 112221451 A CN112221451 A CN 112221451A
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China
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temperature
cooling jacket
jacket layer
reaction kettle
kettle
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CN202011115232.3A
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Chinese (zh)
Inventor
朱桂锋
张倩
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Wuhan Bjm Pharm Inc
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Wuhan Bjm Pharm Inc
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Priority to CN202011115232.3A priority Critical patent/CN112221451A/en
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0006—Controlling or regulating processes
    • B01J19/0013—Controlling the temperature of the process
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0053—Details of the reactor
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/18—Stationary reactors having moving elements inside
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J4/00—Feed or outlet devices; Feed or outlet control devices
    • B01J4/001—Feed or outlet devices as such, e.g. feeding tubes
    • B01J4/007—Feed or outlet devices as such, e.g. feeding tubes provided with moving parts
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2204/00—Aspects relating to feed or outlet devices; Regulating devices for feed or outlet devices
    • B01J2204/002—Aspects relating to feed or outlet devices; Regulating devices for feed or outlet devices the feeding side being of particular interest
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00049—Controlling or regulating processes
    • B01J2219/00051—Controlling the temperature
    • B01J2219/00074—Controlling the temperature by indirect heating or cooling employing heat exchange fluids
    • B01J2219/00087—Controlling the temperature by indirect heating or cooling employing heat exchange fluids with heat exchange elements outside the reactor
    • B01J2219/00094—Jackets

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Accessories For Mixers (AREA)
  • Mixers Of The Rotary Stirring Type (AREA)

Abstract

The invention discloses a low-temperature reaction device for preparing a sitagliptin phosphate intermediate, which comprises the following steps: the reaction kettle is provided with a reactant inlet on the kettle cover, the upper end of the reactant inlet is provided with a motor for driving the reactant inlet to rotate, the lower end of the reactant inlet is provided with a distributor, the bottom of the reaction kettle is provided with a product outlet, and the product outlet is provided with a valve; the stirring assembly comprises a stirring shaft which is arranged on the kettle cover in a penetrating way and is positioned in the reaction kettle, a plurality of groups of stirring blades which are uniformly arranged on the stirring shaft at intervals, and a motor for driving the stirring shaft to rotate; a temperature control assembly comprising a thermocouple and a temperature controller; the cooling assembly comprises a cooling jacket layer, a refrigerator, a mechanical pump, a valve and a flowmeter; and the heat preservation layer is sleeved outside the cooling jacket layer. The invention has the characteristics of high use safety, low requirement on equipment and constant control of reaction temperature.

Description

Low-temperature reaction device for preparing sitagliptin phosphate intermediate
Technical Field
The invention relates to a low-temperature reaction device. More particularly, the invention relates to a low-temperature reaction device for preparing a sitagliptin phosphate intermediate.
Background
Diabetes is largely classified into type 1 diabetes and type 2 diabetes. Type 1 diabetes, also known as insulin-dependent diabetes, is an autoimmune disease, and under the combined action of various factors, the body is immune intolerant to various antigen components of insulin, resulting in absolute deficiency of insulin; type 2 diabetes, also known as non-insulin dependent diabetes, is diabetes that has some degree of insulin secretion, but the degree varies widely, ranging from significant insulin resistance with insulin deficiency to insulin secretion deficiency with insulin resistance. Type 2 diabetes is mainly characterized by a decrease in insulin secretion from the islet beta cells and a decrease in insulin action, i.e., insulin resistance. Diabetes patients are mainly type 2 diabetes, accounting for over 90 percent of the patients, and the patients are the most common type of diabetes.
Sitagliptin phosphate has become increasingly popular as a new antidiabetic agent. 3- (trifluoromethyl) -5,6,7, 8-tetrahydro [1,2,4] triazolo [4, 3-alpha ] piperazine hydrochloride is an important intermediate for synthesizing a drug for treating type 2 diabetes, namely sitagliptin phosphate, and in the process of synthesizing 3- (trifluoromethyl) -5,6,7, 8-tetrahydro [1,2,4] triazolo [4, 3-alpha ] piperazine hydrochloride, one step of reaction is that ethylenediamine and 2-chloromethyl-5-trifluoromethyl-1, 3, 4-oxadiazole react at low temperature to generate N- [ (2Z) -piperazine-2-subunit ] trifluoroacetyl hydrazine. The current technology for realizing low temperature is generally realized by means of liquid nitrogen or ice water bath. The liquid nitrogen cooling technology has the characteristics of poor safety, high cost and high equipment requirement, but the lowest temperature is twenty ℃ below zero when the sitagliptin phosphate intermediate is prepared, and the liquid nitrogen cooling technology is used for achieving the temperature, so that resources are wasted to a certain extent; the method using the ice-water bath has the disadvantage that the temperature is not easy to control to be constant.
Disclosure of Invention
An object of the present invention is to solve at least the above problems and to provide at least the advantages described later.
The invention also aims to provide a low-temperature reaction device for preparing the sitagliptin phosphate intermediate, which has the advantages of enabling reactants to be uniformly mixed and stirred; the reaction temperature is controlled to be constant; high use safety, low cost and low requirement on equipment.
To achieve these objects and other advantages in accordance with the present invention, there is provided a low temperature reaction apparatus for preparing a sitagliptin phosphate intermediate, comprising:
the reaction kettle is a cylinder with a kettle cover, a reactant inlet is formed in the kettle cover, a motor for driving the reactant inlet to rotate is arranged at the upper end of the reactant inlet, a distributing device is arranged at the lower end of the reactant inlet, bulges extending towards the interior of the reaction kettle are uniformly arranged on the inner wall of the reaction kettle at intervals, a product outlet is formed in the bottom of the reaction kettle, and a valve is arranged on the product outlet; the stirring assembly comprises a stirring shaft which is arranged on the kettle cover in a penetrating manner and is positioned in the reaction kettle, a plurality of groups of stirring blades which are uniformly arranged on the stirring shaft at intervals, and a motor for driving the stirring shaft to rotate, wherein the stirring blades comprise a first fusiform blade and a second fusiform blade which are arranged vertically, the head end of the first fusiform blade is connected with the stirring shaft, and the tail end of the first fusiform blade is connected with the middle part of the second fusiform blade; the temperature control assembly comprises a thermocouple and a temperature controller, the thermocouple is arranged on the kettle cover in a penetrating manner, the temperature controller is arranged at the upper end of the thermocouple, and the lower end of the thermocouple is arranged in the reaction kettle; the cooling assembly comprises a cooling jacket layer, a refrigerator, a mechanical pump, a valve and a flowmeter, wherein the cooling jacket layer is sleeved outside the reaction kettle, a cavity is formed inside the cooling jacket layer, a cooling substance is arranged in the cavity, the lower end of the outer wall of the cooling jacket layer is provided with a cooling jacket layer inlet, the upper end of the outer wall of the cooling jacket layer is provided with a cooling jacket layer outlet, and the refrigerator, the mechanical pump, the valve and the flowmeter are sequentially connected from the outlet of the cooling jacket layer to the inlet of the cooling jacket layer according to the flow direction of the cooling substance; and the heat preservation layer is sleeved outside the cooling jacket layer.
Preferably, the kettle cover is arc-shaped, and the inner wall of the reaction kettle and the surface of the protrusion are in a sawtooth shape.
Preferably, the shape of distributing device is the loudspeaker form that big end down, the lower terminal surface of distributing device is the slope form, be equipped with in the distributing device and be on a parallel with the baffle of terminal surface under the distributing device, the distributing device down the terminal surface with all the interval is equipped with a plurality of round holes on the baffle.
Preferably, each group of the stirring blades of the stirring assembly and the protrusions of the reaction kettle are arranged in the reaction kettle at intervals in a crossing manner.
Preferably, the temperature of the temperature reducing substance is-100 ℃ to-5 ℃.
Preferably, the flow rate of the cooling substance is 0.5cm3/s～300cm3/s。
Preferably, the cooling substance is one or a combination of several of ethanol, ethylene glycol, methanol and freon.
Preferably, a filler is arranged in the heat insulation layer, and the filler is a mixture of quartz wool and foam in a certain proportion.
The invention at least comprises the following beneficial effects:
firstly, the reactants are uniformly mixed and stirred; the reaction temperature is controlled to be constant; high use safety, low cost and low requirement on equipment.
Second, the motor drive reactant entry that reactant entry upper end set up rotates to can drive and set up in the distributing device of reactant entry lower extreme and rotate, make the reactant enter into reation kettle under the effect of gravity and centrifugal force simultaneously, and then make the reactant can mix more even when adding.
Thirdly, bulges extending towards the interior of the reaction kettle are uniformly arranged on the inner wall of the reaction kettle at intervals, so that the inner surface area of the reaction kettle can be increased; the cooling material passes through the cooling jacket layer at a certain flow rate, and the flow rate of the cooling material is controlled, so that the temperature of the reaction kettle system is the temperature required by the experiment.
Additional advantages, objects, and features of the invention will be set forth in part in the description which follows and in part will become apparent to those having ordinary skill in the art upon examination of the following or may be learned from practice of the invention.
Drawings
Fig. 1 is a schematic perspective view of the whole device according to one embodiment of the present invention;
FIG. 2 is a schematic perspective view of a reactant inlet according to one embodiment of the present invention;
Detailed Description
The present invention is further described in detail below with reference to the attached drawings so that those skilled in the art can implement the invention by referring to the description text.
As shown in fig. 1-2, the invention provides a low-temperature reaction device for preparing a sitagliptin phosphate intermediate, which comprises:
the reaction kettle 5 is a cylinder with a kettle cover, a reactant inlet 8 is arranged on the kettle cover, a motor 7 for driving the reactant inlet 8 to rotate is arranged at the upper end of the reactant inlet 8, a distributor 9 is arranged at the lower end of the reactant inlet 8, bulges extending towards the interior of the reaction kettle 5 are uniformly arranged on the inner wall of the reaction kettle 5 at intervals, a product outlet 18 is arranged at the bottom of the reaction kettle 5, and a valve 17 is arranged on the product outlet 18; the stirring assembly 6 comprises a stirring shaft which is arranged on the kettle cover in a penetrating manner and is positioned in the reaction kettle, a plurality of groups of stirring blades which are uniformly arranged on the stirring shaft at intervals, and a motor for driving the stirring shaft to rotate, wherein the stirring blades comprise a first fusiform blade and a second fusiform blade which are arranged vertically, the head end of the first fusiform blade is connected with the stirring shaft, and the tail end of the first fusiform blade is connected with the middle part of the second fusiform blade; the temperature control assembly comprises a thermocouple 4 and a temperature controller 2, the thermocouple 4 penetrates through the kettle cover, the temperature controller 2 is arranged at the upper end of the thermocouple 4, and the lower end of the thermocouple 4 is arranged in the reaction kettle; the cooling assembly comprises a cooling jacket layer 3, a refrigerator 11, a mechanical pump 12, a valve 13 and a flowmeter 14, wherein the cooling jacket layer 3 is sleeved outside the reaction kettle 5, the inside of the cooling jacket layer 3 is a cavity, a cooling substance is arranged in the cavity, a cooling jacket layer inlet 15 is arranged at the lower end of the outer wall of the cooling jacket layer 3, a cooling jacket layer outlet 10 is arranged at the upper end of the outer wall of the cooling jacket layer 3, and the refrigerator 11, the mechanical pump 12, the valve 13 and the flowmeter 14 are sequentially connected from the outlet 10 of the cooling jacket layer to the inlet 15 of the cooling jacket layer according to the flow direction of the cooling substance; and the heat-insulating layer 16 is sleeved outside the cooling jacket layer 3.
In the technical scheme, the whole device mainly comprises a reaction kettle 5, a stirring assembly 6, a temperature control assembly, a cooling assembly and a heat preservation layer 16. The reaction kettle 5 is a cylinder and mainly comprises a kettle cover, a reactant inlet 8, a distributor 9 and a product outlet 18. The upper end of reactant entry 8 is provided with drive reactant entry pivoted motor 7, the lower extreme of reactant entry 8 is provided with distributing device 9, the inner wall of reation kettle 5 is evenly provided with the arch to the inside extension of reation kettle 5 at an interval, be provided with valve 17 on the product export 18. And the stirring assembly 6 mainly comprises a stirring shaft, a motor for driving the stirring shaft to rotate and a plurality of groups of stirring blades. The stirring shaft penetrating through the kettle cover is positioned inside the reaction kettle 5; the multiple groups of stirring blades are uniformly arranged on the stirring shaft at intervals. The temperature control assembly comprises a thermocouple 4 and a temperature controller 2, the temperature controller 2 is arranged at the upper end of the thermocouple 4 on the kettle cover in a penetrating mode, and the lower end of the temperature control assembly is arranged inside the reaction kettle 5. The cooling assembly comprises a cooling jacket layer 3, a refrigerator 11, a mechanical pump 12, a valve 13 and a flowmeter 14. The export 10 of cooling jacket layer set up in the upper end of 3 outer walls of cooling jacket layer, the entry 15 of cooling jacket layer set up in the lower extreme of cooling jacket layer 3. And a cooling substance is arranged in the inner cavity of the cooling jacket layer 3 sleeved outside the reaction kettle 5. The refrigerator 11, the mechanical pump 12, the valve 13 and the flowmeter 14 are sequentially connected from the outlet 10 of the cooling jacket layer to the inlet 15 of the cooling jacket layer according to the flowing direction of the cooling substance. The heat-insulating layer 16 is sleeved outside the cooling jacket layer 3. The specific using method comprises the following steps: firstly, the cooling material passes through the cooling jacket layer 3 from the inlet 15 of the cooling jacket layer at a certain flow velocity, flows through the cooling jacket layer 3 and then reaches the outlet 10 of the cooling jacket layer, so that the temperature of the reaction system is controlled to be the experimental temperature. The actual temperature is read from the temperature controller 2 in the temperature control assembly. And then, when the temperature of the reaction system is the temperature required by the experiment and is kept constant, sequentially adding reactants into a reactant inlet 8 of the reaction kettle 5, opening a motor 7 for driving the reactant inlet 8 to rotate, and driving a distributor 9 to rotate, so that the reactants are added into the reaction kettle 5. Then, the motor in the stirring assembly 6 for driving the stirring shaft to rotate is turned on, so that the stirring assembly starts to work, and the reaction starts to progress. Finally, after the reaction is finished, the valve 17 on the product outlet 18 is opened to discharge the substances in the reaction kettle 5. Reation kettle 5's kettle cover department is provided with reactant entry 8, the motor 7 that the upper end of reactant entry 8 set up can drive reactant entry 8 and rotate to can drive and set up in distributor 9 of 8 lower extremes of reactant entry and rotate, and then make the reactant can mix more even when adding. Even interval is provided with multiunit stirring paddle on the (mixing) shaft, can make reation kettle's stirring more even, the reaction is more thorough. The inner wall of reation kettle 5 is provided with the arch of directional reation kettle 5 inside extension at even interval, can increase reation kettle 5's internal surface area is favorable to controlling reation kettle 5's temperature better and maintains invariable, improves reation kettle 5's refrigeration effect. The cover is located outside reation kettle 5 the inside of cooling jacket layer 3 is the cavity, be provided with the cooling material in the cavity, the cooling material passes through with certain velocity of flow cooling jacket layer 3, control the velocity of flow of cooling material, thereby control the temperature of reaction system, and then make the temperature of reaction system be the required temperature of experiment. The heat-insulating layer 16 is sleeved outside the cooling jacket layer 3, and a filler is filled in the heat-insulating layer 16, wherein the filler is a mixture of quartz wool and foam in a certain proportion, so that the temperature of the reaction system is kept constant.
In another technical scheme, the kettle cover is circular-arc, reation kettle 5's inner wall with bellied surface is the cockscomb structure, can increase reation kettle 5's internal surface area is favorable to controlling reation kettle 5's temperature better and maintains invariable, improves reation kettle 5's refrigeration effect.
In another kind of technical scheme, the shape of distributing device 9 is big end down's loudspeaker form, the lower terminal surface of distributing device 9 is the slope form, be equipped with in the distributing device 9 and be on a parallel with the baffle of terminal surface under the distributing device 9, distributing device 9 the terminal surface down with all the interval is equipped with a plurality of round holes on the baffle. Reation kettle 5's kettle cover department is provided with reactant entry 8, the motor 7 that the upper end of reactant entry 8 set up can drive reactant entry 8 and rotate to can drive and set up in distributor 9 of 8 lower extremes of reactant entry and rotate, thereby make the reactant can mix when adding more even. The lower end face of the distributing device 9 and the partition plate are arranged in an inclined shape, so that the residues of reactants on the lower end face of the distributing device and the partition plate during the step of adding the reactants can be effectively reduced, and the reactants can be ensured to participate in the reaction as much as possible. The reactant added through the reactant inlet 8 firstly passes through the partition plate of the distributing device 9 and then passes through the lower end face of the distributing device 9; the reactant is acted by gravity and centrifugal force simultaneously when passing through the baffle plate and the lower end face of the distributing device 9, so that the added reactant is sufficiently dispersed when passing through the reactant inlet 8, and the reactant entering the reaction kettle is sufficiently reacted.
In another technical scheme, each group of the stirring blades of the stirring assembly 6 and the protrusions of the reaction kettle are arranged in the reaction kettle 5 at intervals in a crossing manner, so that the stirring blades and the protrusions do not collide with each other, and the stirring blades and the protrusions can respectively play a role of themselves well.
In another technical scheme, the temperature of the temperature reducing substance is-100 ℃ to-5 ℃. The temperature reducing substance is maintained in a certain temperature range, so that the temperature reducing substance can provide the temperature required by the experiment for the reaction system.
In another technical scheme, the flow of the cooling substance is 0.5cm3/s～300cm3And s. When the cooling material with a certain temperature passes through the cooling jacket layer at different flow rates, the temperature of the reaction system can be different. Therefore, the method can be applied according to different experimental requirementsAnd adjusting the flow rate of the temperature reducing substance to control the temperature of the reaction system, so that the temperature of the reaction system is the temperature required by the experiment.
In another technical scheme, the cooling substance is one or a combination of several of ethanol, glycol, methanol and freon. The temperature range which can be controlled and is obtained after different combinations of the temperature reducing substances are not needed, and the combinations of the temperature reducing substances which are suitable for experimental conditions can be selected according to the requirements of the experimental conditions.
In another technical scheme, a filler is arranged in the heat-insulating layer 16, and the filler is a mixture of quartz wool and foam in a certain proportion, so that the temperature of the reaction system is kept constant.
While embodiments of the invention have been described above, it is not limited to the applications set forth in the description and the embodiments, which are fully applicable in various fields of endeavor to which the invention pertains, and further modifications may readily be made by those skilled in the art, it being understood that the invention is not limited to the details shown and described herein without departing from the general concept defined by the appended claims and their equivalents.

Claims (8)

1. A low-temperature reaction device for preparing a sitagliptin phosphate intermediate is characterized by comprising the following components:
the reaction kettle is a cylinder with a kettle cover, a reactant inlet is formed in the kettle cover, a motor for driving the reactant inlet to rotate is arranged at the upper end of the reactant inlet, a distributing device is arranged at the lower end of the reactant inlet, bulges extending towards the interior of the reaction kettle are uniformly arranged on the inner wall of the reaction kettle at intervals, a product outlet is formed in the bottom of the reaction kettle, and a valve is arranged on the product outlet;
the stirring assembly comprises a stirring shaft which is arranged on the kettle cover in a penetrating manner and is positioned in the reaction kettle, a plurality of groups of stirring blades which are uniformly arranged on the stirring shaft at intervals, and a motor for driving the stirring shaft to rotate, wherein the stirring blades comprise a first fusiform blade and a second fusiform blade which are arranged vertically, the head end of the first fusiform blade is connected with the stirring shaft, and the tail end of the first fusiform blade is connected with the middle part of the second fusiform blade;
the temperature control assembly comprises a thermocouple and a temperature controller, the thermocouple is arranged on the kettle cover in a penetrating manner, the temperature controller is arranged at the upper end of the thermocouple, and the lower end of the thermocouple is arranged in the reaction kettle;
the cooling assembly comprises a cooling jacket layer, a refrigerator, a mechanical pump, a valve and a flowmeter, wherein the cooling jacket layer is sleeved outside the reaction kettle, a cavity is formed inside the cooling jacket layer, a cooling substance is arranged in the cavity, the lower end of the outer wall of the cooling jacket layer is provided with a cooling jacket layer inlet, the upper end of the outer wall of the cooling jacket layer is provided with a cooling jacket layer outlet, and the refrigerator, the mechanical pump, the valve and the flowmeter are sequentially connected from the outlet of the cooling jacket layer to the inlet of the cooling jacket layer according to the flow direction of the cooling substance;
and the heat preservation layer is sleeved outside the cooling jacket layer.
2. The low-temperature reaction device for preparing the sitagliptin phosphate intermediate as claimed in claim 1, wherein the kettle cover is arc-shaped, and the inner wall of the reaction kettle and the surface of the protrusion are saw-toothed.
3. The low-temperature reaction device for preparing the sitagliptin phosphate intermediate as claimed in claim 1, wherein the shape of the distributing device is a horn shape with a small top and a big bottom, the lower end face of the distributing device is an inclined shape, a baffle plate parallel to the lower end face of the distributing device is arranged in the distributing device, and a plurality of round holes are arranged on the lower end face of the distributing device and the baffle plate at intervals.
4. The low-temperature reaction device for preparing the sitagliptin phosphate intermediate according to claim 1, wherein each group of the stirring blades of the stirring assembly is arranged inside the reaction kettle in a crossing and spaced manner with the protrusions of the reaction kettle.
5. The low-temperature reaction device for preparing the sitagliptin phosphate intermediate as claimed in claim 1, wherein the temperature of the temperature reducing substance is-100 ℃ to-5 ℃.
6. The low-temperature reaction device for preparing sitagliptin phosphate intermediate according to claim 1, wherein the flow rate of the temperature reducing substance is 0.5cm3/s～300cm3/s。
7. The low-temperature reaction device for preparing the sitagliptin phosphate intermediate as claimed in claim 1, wherein the cooling substance is one or a combination of several of ethanol, ethylene glycol, methanol and freon.
8. The low-temperature reaction device for preparing the sitagliptin phosphate intermediate according to claim 1, wherein a filler is arranged in the heat-insulating layer, and the filler is a mixture of quartz wool and foam in a certain proportion.
CN202011115232.3A 2020-10-19 2020-10-19 Low-temperature reaction device for preparing sitagliptin phosphate intermediate Pending CN112221451A (en)

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CN202011115232.3A CN112221451A (en) 2020-10-19 2020-10-19 Low-temperature reaction device for preparing sitagliptin phosphate intermediate

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CN202011115232.3A CN112221451A (en) 2020-10-19 2020-10-19 Low-temperature reaction device for preparing sitagliptin phosphate intermediate

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3039859A (en) * 1956-10-12 1962-06-19 Lechler Paul Fa Apparatus for pretreating chemically reacting materials
CN207493695U (en) * 2017-11-15 2018-06-15 湖南浩润科技有限公司 A kind of reaction kettle
CN208912052U (en) * 2018-04-09 2019-05-31 湖南三森高科新材料科技有限公司 A kind of cooling reaction kettle
CN209237960U (en) * 2018-12-13 2019-08-13 四川安县银河机械制造有限责任公司 A kind of small-size multifunction reaction kettle
CN209814805U (en) * 2019-04-19 2019-12-20 南京阿克赛斯科技有限公司 In-bin material discharger with anti-blocking effect

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3039859A (en) * 1956-10-12 1962-06-19 Lechler Paul Fa Apparatus for pretreating chemically reacting materials
CN207493695U (en) * 2017-11-15 2018-06-15 湖南浩润科技有限公司 A kind of reaction kettle
CN208912052U (en) * 2018-04-09 2019-05-31 湖南三森高科新材料科技有限公司 A kind of cooling reaction kettle
CN209237960U (en) * 2018-12-13 2019-08-13 四川安县银河机械制造有限责任公司 A kind of small-size multifunction reaction kettle
CN209814805U (en) * 2019-04-19 2019-12-20 南京阿克赛斯科技有限公司 In-bin material discharger with anti-blocking effect

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Application publication date: 20210115