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Recovery method of ethyl 2-(2-aminothiazole-4-yl)-2-methoxyiminoacetate

A technology of ethyl aminothiaxamate and a recovery method, which is applied in the field of medicine, can solve problems such as affecting product yield, low atom economy, and non-compliance with trends, and achieve high industrial value, simple process, and considerable profits.

Inactive Publication Date: 2020-12-01
SHANDONG JINCHENG PHARMACCUTICAL CHEM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Trans-aminothioxamic acid ethyl ester is viscous and oily and difficult to handle. It can only enter the waste water and waste residues for centralized incineration with the cyclization mother liquor. On the one hand, it causes high environmental protection pressure and does not conform to the current trend of green chemistry; rate, low atom economy
At present, there are few reports about the recovery and treatment scheme of trans-aminothioxamic acid ethyl ester

Method used

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  • Recovery method of ethyl 2-(2-aminothiazole-4-yl)-2-methoxyiminoacetate
  • Recovery method of ethyl 2-(2-aminothiazole-4-yl)-2-methoxyiminoacetate
  • Recovery method of ethyl 2-(2-aminothiazole-4-yl)-2-methoxyiminoacetate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] (1) Take 1000 g of the cyclization mother liquor after the separation of industrial materials, and distill methanol under negative pressure, control the temperature to ≤30°C, and the vacuum degree to ≤-0.095MPa. After distillation, the weight of the residual liquid was 728.4g, and 350.5g of dichloromethane was added to stir and extract. After the layers were separated, the dichloromethane phase was spin-dried to obtain 84.7g of trans-aminothioxamic acid crude product.

[0037] (2) The trans-aminothioxamic acid ethyl ester crude product that step (1) obtains is dropped in the ethanol aqueous solution of 254.5g 95wt.%, after stirring and dissolving, add 25.6g p-toluenesulfonic acid, 18.7g propionaldehyde, be warming up to reflux, insulation reaction After 3.5h, an ethanol solution containing ethyl 2-(2-aminothiazol-4-yl)glyoxylate intermediate was obtained.

[0038] (3) In the ethanol solution containing 2-(2-aminothiazol-4-yl) ethyl glyoxylate intermediate obtained in st...

Embodiment 2

[0045] (1) Take 1000 g of the cyclization mother liquor after the separation of industrial materials, and distill methanol under negative pressure, control the temperature to ≤30°C, and the vacuum degree to ≤-0.095MPa. After distillation, the weight of the residual liquid was 716.4 g, and 360.5 g of n-hexane was added to stir and extract, and after the layers were separated, the n-hexane phase was spin-dried to obtain 82.5 g of crude product of trans-aminothioxamic acid ethyl ester.

[0046] (2) drop the trans-aminothioxamic acid ethyl ester crude product that step (1) obtains into 262.8g 95wt.% ethanol aqueous solution, add 24.6g p-toluenesulfonic acid, 18.7g propionaldehyde after stirring and dissolving, heat up to reflux, insulation reaction After 4h, an ethanol solution containing ethyl 2-(2-aminothiazol-4-yl)glyoxylate intermediate was obtained.

[0047] (3) In the ethanol solution containing 2-(2-aminothiazol-4-yl) ethyl glyoxylate intermediate obtained in step (2), add ...

Embodiment 3

[0054] (1) Take 1000 g of the cyclization mother liquor after the separation of industrial materials, and distill methanol under negative pressure, control the temperature to ≤30°C, and the vacuum degree to ≤-0.095MPa. After distillation, the weight of the residual liquid was 720.5g, and 380.9g of ethyl acetate was added to stir and extract. After the layers were separated, the ethyl acetate phase was spin-dried to obtain 89.7g of crude trans-aminothioxamic acid ethyl ester.

[0055] (2) The trans-aminothioxamic acid ethyl ester crude product that step (1) obtains is dropped in the ethanol aqueous solution of 270.8g 95wt.%, after stirring and dissolving, add 35.3g p-toluenesulfonic acid, 22.3g propionaldehyde, be warming up to reflux, insulation reaction After 5h, an ethanol solution containing ethyl 2-(2-aminothiazol-4-yl)glyoxylate intermediate was obtained.

[0056] (3) In the ethanol solution containing 2-(2-aminothiazol-4-yl) ethyl glyoxylate intermediate obtained in step (...

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Abstract

The invention belongs to the technical field of medicines, and particularly relates to a recovery method of ethyl 2-(2-aminothiazole-4-yl)-2-methoxyiminoacetate. The method comprises the following steps: under the action of an acidic catalyst, reacting a crude ethyl trans-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetate product separated from cyclization mother liquor with propionaldehyde to obtainan ethyl 2-(2-aminothiazol-4-yl)glyoxylate intermediate; and reacting the ethyl 2-(2-aminothiazol-4-yl)glyoxylate intermediate with methoxylamine hydrochloride, so as to prepare the ethyl 2-(2-aminothiazole-4-yl)-2-methoxyiminoacetate. According to the method disclosed by the invention, ethyl trans-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetate is converted into ethyl cis-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetate, so that the atom utilization rate of the process is greatly improved, and meanwhile, the quality of the recovered product meets the downstream use standard; and the content of organic impurities in the cyclization mother liquor is reduced, so a large amount of viscous industrial solid waste is avoided, the environment-friendly treatment difficulty is reduced, and the methodconforms to the current development direction of green chemistry.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a method for recovering ethyl aminothiaxamate. Background technique [0002] Ethyl aminothioxamate is an important pharmaceutical intermediate, mainly used in the synthesis of side chains of cefotaxime sodium, ceftriaxone, ceftazidine, ceftriaxone, etc. At present, there are many reports on the synthesis method of ethyl acetoxamic acid, mainly using ethyl acetoacetate as the starting material, and obtaining 4-chloro / bromo-2-methoxyiminoacetoacetic acid through oximation, methylation, halogenation and other processes Ethyl ester; in alcoholic water solvent, 4-chloro / bromo-2-methoxyiminoacetoacetate ethyl ester and thiourea cyclization obtain ethyl aminothioxamic acid ester, and its reaction process is as follows: [0003] [0004] Since the first step oximation reaction is carried out in an acidic environment, the product 2-methoxyiminoacetoacetate ethyl ester wil...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D277/593
CPCC07D277/593Y02P20/584
Inventor 赵奇孙兴孟宪强董玉龙
Owner SHANDONG JINCHENG PHARMACCUTICAL CHEM CO LTD