Method for preparing (Z)-5-amino-alpha-(ethoxy imino group)-1, 2, 4-thiadiazole-3-acetic acid

An ethoxyimino, thiadiazole technology, applied in the direction of organic chemistry and the like, can solve the problems of large environmental goals, many steps, long routes, etc., and achieves the effects of fewer synthesis steps, low cost and less pollution

Active Publication Date: 2014-05-21
山西海泰电子材料有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The existing synthetic route uses 2-cyanoacetamide as a raw material, which is first oximated with sodium nitrite, then ethoxylated and then dehydrated, and finally added with ammonia water, brominated, cyclized, and hydrolyzed to obtain the product. Long, many steps, and more toxic phosphorus oxychloride is used, which is more harmful to the environment

Method used

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  • Method for preparing (Z)-5-amino-alpha-(ethoxy imino group)-1, 2, 4-thiadiazole-3-acetic acid
  • Method for preparing (Z)-5-amino-alpha-(ethoxy imino group)-1, 2, 4-thiadiazole-3-acetic acid
  • Method for preparing (Z)-5-amino-alpha-(ethoxy imino group)-1, 2, 4-thiadiazole-3-acetic acid

Examples

Experimental program
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Effect test

Embodiment 1

[0036] 1) Add 1 mol of malononitrile, 1 mol of water and 2 mol of glacial acetic acid into a three-necked flask, cool down to 0°C, add 4 mol of sodium nitrite, react at 0°C for 3 hours to obtain reaction product A, adjust the pH value of reaction product A 2. Then extract the reaction product A with 100g of ethyl acetate each time, and extract three times in total. Combine the three extraction phases and remove the solvent by rotary evaporation under reduced pressure, that is, in a water bath at 40°C and a rotary evaporator with a vacuum of 0.08MPa The solvent was removed in the middle to obtain a reddish-brown liquid, namely compound A;

[0037] 2) Under the protection of argon, add 1 mol of compound A to the three-necked flask, cool down to 5°C, add 3 mol of triethylamine, stir for 1 hour, then add 2 mol of bromoethane, and then rise to room temperature to dissolve the bromoethane, and then React at 5°C for 3 hours to obtain the reaction product B, add 300g of water to the r...

Embodiment 2

[0042] 1) Add 1 mol of malononitrile, 2 mol of water and 3 mol of glacial acetic acid into the three-necked flask, cool down to 5°C, add 2 mol of sodium nitrite, and react at 5°C for 4 hours to obtain the reaction product A, adjust the pH value of the reaction product A 2. Then extract the reaction product A with 100g of ethyl acetate each time, and extract three times in total. After combining the three extraction phases, the solvent is removed by rotary evaporation under reduced pressure, that is, in a water bath at 30°C and a rotary evaporator with a vacuum of 0.07MPa The solvent was removed in the middle to obtain a reddish-brown liquid, namely compound A;

[0043] 2) Under the protection of neon gas, add 1 mol of compound A to the three-necked flask, cool down to 0°C, add 2 mol of triethylamine, stir for 2 hours, then add 3 mol of bromoethane, and then rise to room temperature to dissolve the bromoethane, and then React at 0°C for 3.5 hours to obtain the reaction product B,...

Embodiment 3

[0048] 1) Add 1 mol of malononitrile, 1.5 mol of water and 2.5 mol of glacial acetic acid into a three-necked flask, cool down to 2°C, add 3 mol of sodium nitrite, react at 2°C for 5 hours to obtain reaction product A, adjust the pH of reaction product A The value is 2, and then the reaction product A is extracted three times with 100g ethyl acetate at a time, and the extraction phases of the three times are combined and then the solvent is removed by rotary evaporation under reduced pressure, that is, in a water bath at 35°C and a vacuum of 0.06MPa. The solvent was removed in an evaporator to obtain a reddish-brown liquid, namely compound A;

[0049] 2) Under the protection of nitrogen, add 1 mol of compound A to the three-necked flask, cool down to 2°C, add 2.5 mol of triethylamine, stir for 1.5 h, then add 2.5 mol of diethyl sulfate, and then rise to room temperature to make diethyl sulfate Dissolve, then react at 2°C for 3 h to obtain reaction product B, add 300 g of water...

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Abstract

The invention discloses a method for preparing (Z)-5-amino-alpha-(ethoxy imino group)-1, 2, 4-thiadiazole-3-acetic acid. The method comprises steps of firstly, carrying out oximation reaction on malononitrile and sodium nitrite under the action of acetic acid so as to obtain a compound A, then carrying out Williamson synthesis on the compound A and bromoethane or diethyl sulfate under alkaline condition, so as to obtain a compound B, then carrying out amidine reaction on the compound B and ammonia water, so as to obtain a compound C, carrying out cyclization reaction on the compound C and potassium rhodanide for ring closing so as to obtain a compound D, and finally, hydrolyzing the compound D under the action of a strong base, so as to obtain (Z)-5-amino-alpha-(ethoxy imino group)-1, 2, 4-thiadiazole-3-acetic acid. The method has few synthesis steps, has low cost, uses the materials which are cheap and easy to obtain, is beneficial to industrial production, and has light contamination; the purity of the product can reach 99%, so that synthesis of high-purity ceftaroline fosamil in the subsequent step is guaranteed.

Description

technical field [0001] The invention belongs to the field of chemical synthesis, and in particular relates to a preparation method of (Z)-5-amino-α-(ethoxyimino)-1,2,4-thiadiazole-3-acetic acid. Background technique [0002] Ceftaroline is a fifth-generation cephalosporin antibiotic that has potent antibacterial activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), while maintaining the same Cephalosporins have comparable activity against Gram-positive bacteria, so the industrialization of their 7-side chain synthesis is of great significance. The existing synthetic route uses 2-cyanoacetamide as a raw material, which is first oximated with sodium nitrite, then ethoxylated and then dehydrated, and finally added with ammonia water, brominated, cyclized, and hydrolyzed to obtain the product. Long, many steps, and more toxic phosphorus oxychloride is used, which has a greater impact on the environment. Contents of the inventio...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D291/04
CPCC07D285/08
Inventor 王作弟
Owner 山西海泰电子材料有限公司
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