Preparation method for cefradine

A technology of cephradine and aminodeacetoxy cephalosporanic acid, which is applied in the field of preparation of cephradine, can solve the problems that the catalytic performance of the catalyst cannot be maximized, the price of the catalytic enzyme is expensive, and the stability of the cephradine product is affected, and the preparation method is simple and easy. line, stable product quality, and less pollution

Inactive Publication Date: 2013-04-17
ZHEJIANG ZHEBANG PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] 200480018394.8, the patent application called "the method for preparing cephradine" discloses a kind of preparation method of cephradine, adopts under the effect of enzyme, makes 7-amino deacetoxy cephalosporanic acid (being called for short 7-ADCA) and activated form D-dihydrophenylglycine reaction obtains cephradine, and this method has avoided environmental pollution, but because catalyzing enzyme price is expensive, and selectivity is very strong, and catalytic effect is greatly influenced by external factors such as air temperature, humidity, pH value; Simultaneously In the reaction, there is also the problem of inhibition of the reaction by products and by-products, so that the catalytic performance of the catalyst cannot be maximized.
But when preparing active dihydrophenylglycine, the protective agent used enters the hydrolyzate with the reaction solution, which affects the crystal form of cephradine and the stability of the product

Method used

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  • Preparation method for cefradine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] 1. Condensation

[0034] Add 100g of 7-ADCA, 450ml of dichloromethane, 25g of N-methylacetamide (NMAC) into a 1000ml three-necked flask, then slowly add 83g of hexamethyldisilazane, raise the temperature to 40°C, and react under reflux for 2 hours to obtain 7- ADCA silicate (that is, obtain the first solution);

[0035] Add 300ml of dichloromethane and 110g of dihydrophenylglycine chloride hydrochloride into a 500ml three-necked flask, and cool down to -30°C (the second solution is obtained);

[0036] Combine the obtained 7-ADCA silicon ester compound and the dissolved dihydrophenylglycine acid chloride hydrochloride in a 1200ml three-neck flask, conduct condensation reaction at -15°C for 1 hour, then raise the temperature to 0°C for condensation reaction for 3 hours, and the condensation reaction Finish.

[0037] 2. Hydrolysis, decolorization, crystallization

[0038] Pour the condensate after the condensation reaction into a 2000ml beaker, add 300ml of purification...

Embodiment 2

[0047] 1. Condensation

[0048] Add 100g of 7-ADCA, 450ml of dichloromethane, and 25g of N-methylacetamide (NMAC) into a 1000ml three-necked flask, then slowly add 83g of hexamethyldisilazane, raise the temperature to 40°C, and react under reflux for 3 hours to obtain 7- ADCA silicate (that is, obtain the first solution);

[0049] Add 300ml of dichloromethane and 110g of dihydrophenylglycine chloride hydrochloride into a 500ml three-necked flask, and cool down to -10°C (the second solution is obtained);

[0050] Combine the obtained 7-ADCA silicon ester compound and the dissolved dihydrophenylglycine acid chloride hydrochloride in a 1200ml three-necked flask, conduct a condensation reaction at -10°C for 1 hour, then heat up to 10°C for 3 hours, and the condensation reaction Finish.

[0051] 2. Hydrolysis, decolorization, crystallization

[0052] Pour the condensate after the condensation reaction into a 2000ml beaker, add 300ml of purification under stirring, stir evenly, adj...

Embodiment 3

[0056] 1. Condensation

[0057] Add 90g of 7-ADCA, 450ml of dichloromethane, and 25g of N-methylacetamide (NMAC) into a 1000ml three-necked flask, then slowly add 75g of hexamethyldisilazane, raise the temperature to 40°C, and react under reflux for 2 hours to obtain 7- ADCA silicate (that is, obtain the first solution);

[0058] Add 300ml of dichloromethane and 99g of dihydrophenylglycine chloride hydrochloride into a 500ml three-necked flask, and cool down to -30°C (the second solution is obtained);

[0059] Combine the obtained 7-ADCA silicon ester compound and the dissolved dihydrophenylglycine acid chloride hydrochloride in a 1200ml three-neck flask, conduct condensation reaction at -15°C for 1 hour, then raise the temperature to 0°C for condensation reaction for 3 hours, and the condensation reaction Finish.

[0060] 2. Hydrolysis, decolorization, crystallization

[0061] Pour the condensate after the condensation reaction into a 2000ml beaker, add 300ml of purificati...

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Abstract

The invention discloses a preparation method for cefradine. The method comprises the following steps: (1) condensation reaction: reacting 7-amino-deacetoxycephalosporanic acid with a silane protective agent in an anhydrous solvent so as to generate silicon-esterified amino-deacetoxycephalosporanic acid, dissolving activated dihydrophenylglycine, and mixing the dissolved dihydrophenylglycine and the silicon-esterified amino-deacetoxycephalosporanic acid to conduct condensation reaction; and (2) hydrolysis, decoloring and crystallization. The preparation method for the cefradine, disclosed by the invention, is simple and easy; the use of the protective agent in the activated dihydrophenylglycine preparing process is avoided; the whole process has the advantages of comparatively mild reaction condition, low raw material cost and less pollution; and the quality of the prepared product is stable.

Description

technical field [0001] The invention relates to an antibacterial drug cephradine, in particular to a preparation method of cephradine. Background technique [0002] Cephradine, alias: Pioneer Reading, Cefradine, Hexcyclamidine, Cefcyclohexene, Cyclohexenamine Cephalosporin, was developed by Bristol-Myers Squibb in 1972. This product is the first-generation semi-synthetic cephalosporin, and its antibacterial effect is similar to that of cephalexin. This product is acid-resistant and can be taken orally, with good absorption and high blood concentration. It is characterized by resistance to β-lactamase, and has rapid and reliable bactericidal effect on drug-resistant Staphylococcus aureus and other bacilli resistant to broad-spectrum antibiotics. Clinically, it is mainly used for infections of the respiratory tract, urinary tract, skin and soft tissues caused by cephradine-sensitive bacteria, such as bronchitis, pneumonia, pyelonephritis, cystitis, ear, nose and throat infect...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D501/22C07D501/04
Inventor 胡宇超曹小朋张勇
Owner ZHEJIANG ZHEBANG PHARMA
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