Purification device of N-(4-fluoro-5-formyl-2-thiazolyl)-acetamide

Abstract

The utility model relates to a purification device of N-(4-fluoro-5-formyl-2-thiazolyl)-acetamide, which comprises a reaction kettle, a pH (potential of hydrogen) sensor is arranged in the reaction kettle, an inlet of the reaction kettle is connected with a high-position dripping tank positioned above the reaction kettle through a flow meter, a balance pipe is arranged between the reaction kettle and the high-position dripping tank, and the balance pipe is connected with the reaction kettle through a flow meter. The other inlet of the reaction kettle is connected with a first diaphragm pump, the outlet of the reaction kettle is respectively connected with a centrifugal machine and a layered sight glass, and the layered sight glass is also connected with the first diaphragm pump. The purification device of N-(4-fluoro-5-formyl-2-thiazolyl)-acetamide disclosed by the utility model has the advantages of short purification time, convenience and simplicity in operation, high purity, high yield and low cost, and meanwhile, environmental protection hazards and safety production risks are reduced.

Description

Technical Field

[0001] The utility model belongs to the technical field of pharmaceutical fine chemical industry, and specifically relates to a purification device for N-(4-fluoro-5-formyl-2-thiazolyl)-acetamide. Background Art

[0002] N-(4-fluoro-5-formyl-2-thiazolyl)-acetamide (structural formula is shown in Formula 1) is an important pharmaceutical intermediate. At present, the general crystallization process of N-(4-fluoro-5-formyl-2-thiazolyl)-acetamide compound is as follows: the extracted organic layer is first concentrated to dryness, water is added to make pulp, centrifuged and dried to obtain a crude dry product, ethylene glycol dimethyl ether is added to the crude product to heat and dissolve, activated carbon is added, filtered while hot, concentrated, water is added to crystallize, and finally centrifuged and dried to obtain the finished product.

[0003]

[0004] The above production process has the following disadvantages:

[0005] (1) The operation process is complicated, and the crude product must be obtained first and then purified.

[0006] (2) The solubility of ethylene glycol dimethyl ether is low, and the amount of solvent used is large. It also needs to be filtered while hot. The filter and pipeline need to be insulated and heated. When the temperature drops, the material will precipitate and block the filter press and pipeline.

[0007] (3) The yield is low and the impurity removal effect is poor. The HPLC purity is around 97%, and some single impurities exceed 0.5%. Summary of the invention

[0008] The utility model aims to provide a purification device for N-(4-fluoro-5-formyl-2-thiazolyl)-acetamide, which has the advantages of short purification time, convenient and simple operation, high purity, high yield and low cost.

[0009] The technical solution adopted by the utility model to solve the above-mentioned problem is: a purification device for N-(4-fluoro-5-formyl-2-thiazolyl)-acetamide, comprising a reactor, a pH sensor is arranged in the reactor, an inlet of the reactor is connected to a high-position dropping tank located above the reactor through a flow meter, a balance pipe is also arranged between the reactor and the high-position dropping tank, another inlet of the reactor is connected to a first diaphragm pump, and the outlet of the reactor is respectively connected to a centrifuge and a stratification sight glass, and the stratification sight glass is also connected to the first diaphragm pump.

[0010] Preferably, the reactor is provided with a jacket outside, and the external jacket is used to control the temperature; and the reactor is provided with a stirring mechanism inside.

[0011] Preferably, the stirring mechanism comprises a stirring shaft, and an anchor stirring paddle and at least one layer of paddle stirring paddles arranged on the stirring shaft, wherein the paddle stirring paddle is located at the upper end of the anchor stirring paddle, and the anchor stirring paddle is located at the end of the stirring shaft.

[0012] Preferably, both the inlet pipeline and the outlet pipeline of the reactor are provided with regulating valves.

[0013] Preferably, the reaction kettle and the high-position dropping tank are both connected to a nitrogen storage tank via a nitrogen pipe.

[0014] Preferably, the high-position dripping tank is also provided with a liquid level meter.

[0015] Preferably, the high-position dripping tank is also connected to a second diaphragm pump.

[0016] Preferably, both the inlet pipeline and the outlet pipeline of the high-position dripping tank are provided with regulating valves.

[0017] Compared with the prior art, the advantages of the utility model are:

[0018] The utility model discloses a purification device for N-(4-fluoro-5-formyl-2-thiazolyl)-acetamide, which has the advantages of short purification time, simple and convenient operation, high efficiency, high product quality (purity can reach 99.5%), high yield and low cost, and reduces environmental hazards and production safety risks. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 It is a schematic diagram of the structure of a purification device for N-(4-fluoro-5-formyl-2-thiazolyl)-acetamide in an embodiment of the utility model.

[0020] Among them: 1 is a reactor, 2 is a pH sensor, 3 is a flow meter, 4 is a high-level dripping tank, 5 is a balance pipe, 6 is a first diaphragm pump, 7 is a centrifuge, 8 is a layered sight glass, 9 is a liquid level meter, and 10 is a second diaphragm pump. Implementation

[0021] The present invention will be described in further detail below in conjunction with the accompanying drawings.

[0022] like Figure 1 As shown, it is a schematic diagram of the structure of the purification device of N-(4-fluoro-5-formyl-2-thiazolyl)-acetamide in this embodiment.

[0023] A purification device for N-(4-fluoro-5-formyl-2-thiazolyl)-acetamide comprises a reactor 1, wherein a jacket is arranged outside the reactor 1, a pH sensor 2 and a stirring mechanism are arranged inside the reactor 1, and the stirring mechanism comprises a stirring shaft, an anchor-type stirring paddle and two layers of paddle-type stirring paddles arranged on the stirring shaft, wherein the paddle-type stirring paddle is located at the upper end of the anchor-type stirring paddle, and the anchor-type stirring paddle is located at the end of the stirring shaft.

[0024] The reactor 1 is connected to the nitrogen storage tank via a nitrogen pipe, and one inlet of the reactor 1 is connected to the high-position dropping tank 4 located above the reactor 1 via a flowmeter 3. A balance pipe 5 is also provided between the reactor 1 and the high-position dropping tank 4, and the balance pipe 5 is respectively connected to the top of the reactor 1 and the top of the high-position dropping tank 4. The high-position dropping tank 4 is also provided with a liquid level gauge 9 for observing the liquid level, and the high-position dropping tank 4 is also connected to a second diaphragm pump 10; another inlet of the reactor 1 is connected to a first diaphragm pump 6, and the outlet of the reactor 1 is respectively connected to a centrifuge 7 and a stratified sight glass 8, and the stratified sight glass 8 is also connected to the first diaphragm pump 6; the inlet pipeline and the outlet pipeline of the reactor 1 are both provided with regulating valves, and the inlet pipeline and the outlet pipeline of the high-position dropping tank 4 are also both provided with regulating valves, and the regulating valves are specifically electromagnetic regulating valves; wherein the pH sensor 2 and the electromagnetic regulating valve are both connected to and controlled by a PLC controller.

[0025] The working process of this embodiment is described in detail below with reference to the accompanying drawings:

[0026] First, nitrogen from a nitrogen storage tank is introduced into the reactor 1 and the high-position dropping tank 4 through a nitrogen pipe, so that the reactor 1 and the high-position dropping tank 4 are in a nitrogen atmosphere, and then an organic phase containing N-(4-fluoro-5-formyl-2-thiazolyl)-acetamide and a sodium bisulfite solution are pumped in through a first diaphragm pump 6. After being fully stirred by a stirring mechanism, N-(4-fluoro-5-formyl-2-thiazolyl)-acetamide and sodium bisulfite are salified, and the mixture is allowed to stand, and then the mixture enters a delamination mirror 8 through the outlet of the reactor 1. The mixture is delaminated through the delamination mirror 8, the water layer is collected, and the organic layer is discarded (impurities without aldehyde groups are not salified and are dissolved in the organic layer, and N-(4-fluoro-5-formyl-2-thiazolyl)-acetamide and sodium bisulfite are salified in the water layer). The water layer is passed through a filter. The first diaphragm pump 6 is used to pump phosphoric acid into the reactor 1. The second diaphragm pump 10 pumps phosphoric acid into the high-position dropping tank 4. The flow meter 3 and the electromagnetic regulating valve on the pipeline connecting the high-position dropping tank 4 and the reactor 1 are opened to make the phosphoric acid in the high-position dropping tank 4 drip into the reactor 1 at a certain speed. The pH sensor 2 in the reactor 1 detects the pH of the reactor 1 in real time, and transmits the pH detection result to the PLC controller until the pH value of the material in the reactor 1 is 1-2. The PLC controller controls the closing of the electromagnetic regulating valve on the pipeline connecting the high-position dropping tank 4 and the reactor 1, cools to 0-5°C, and then enters the centrifuge 7 through the outlet of the reactor 1 for centrifugation, and then is dried to obtain N-(4-fluoro-5-formyl-2-thiazolyl)-acetamide.

[0027] In addition to the above embodiments, the present invention also includes other implementation modes. Any technical solutions formed by equivalent transformation or equivalent replacement should fall within the protection scope of the claims of the present invention.

Claims

1. A purification device for N-(4-fluoro-5-formyl-2-thiazolyl)-acetamide, characterized in that: The invention comprises a reactor (1), wherein a pH sensor (2) is arranged inside the reactor (1), an inlet of the reactor (1) is connected to a high-position dropping tank (4) located above the reactor (1) via a flow meter (3), a balance pipe (5) is also arranged between the reactor (1) and the high-position dropping tank (4), another inlet of the reactor (1) is connected to a first diaphragm pump (6), and an outlet of the reactor (1) is respectively connected to a centrifuge (7) and a stratification sight glass (8), and the stratification sight glass (8) is also connected to the first diaphragm pump (6).

2. The purification device for N-(4-fluoro-5-formyl-2-thiazolyl)-acetamide according to claim 1, characterized in that: The reactor (1) is provided with a jacket on the outside and a stirring mechanism on the inside.

3. The purification device for N-(4-fluoro-5-formyl-2-thiazolyl)-acetamide according to claim 2, characterized in that: The stirring mechanism comprises a stirring shaft and an anchor-type stirring paddle and a paddle-type stirring paddle arranged on the stirring shaft.

4. The purification device for N-(4-fluoro-5-formyl-2-thiazolyl)-acetamide according to claim 1, characterized in that: The inlet pipeline and the outlet pipeline of the reactor (1) are both provided with regulating valves.

5. The purification device for N-(4-fluoro-5-formyl-2-thiazolyl)-acetamide according to claim 1, characterized in that: The reaction kettle (1) and the high-position dropping tank (4) are both connected to a nitrogen storage tank via a nitrogen pipe.

6. The purification device for N-(4-fluoro-5-formyl-2-thiazolyl)-acetamide according to claim 1, characterized in that: The high-position dripping tank (4) is also provided with a liquid level meter (9).

7. The purification device for N-(4-fluoro-5-formyl-2-thiazolyl)-acetamide according to claim 1, characterized in that: The high-position dripping tank (4) is also connected to a second diaphragm pump (10).

8. The purification device for N-(4-fluoro-5-formyl-2-thiazolyl)-acetamide according to claim 1, characterized in that: The inlet pipeline and the outlet pipeline of the high-position dripping tank (4) are both provided with regulating valves.

Images