Method for synthesizing cefepime hydrochloride

A technology of cefepime hydrochloride and its synthesis method, which is applied in the fields of chemical instruments and methods, organic compound/hydride/coordination complex catalyst, organic chemistry, etc., and can solve unfavorable continuity, large-scale industrial production, and harsh reaction conditions , high cost of raw materials and other issues, to achieve the effect of increasing product yield, improving purity, and improving product purity

Inactive Publication Date: 2010-06-16
YIYUAN XINQUAN CHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] For the reported synthetic methods, there are disadvantages of high cost of raw materials, harsh reaction

Method used

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  • Method for synthesizing cefepime hydrochloride

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] 1. Preparation of 7-MPCA

[0023] Add 200ml of dichloromethane, 40ml of hexamethyldisilazane, 0.2ml of iodotrimethylsilane, and 40g of 7-ACA into a three-necked flask, stir and mix well, and heat to reflux for 8 hours under nitrogen protection. After detecting that no ammonia gas is released, cool the solution to 0-5°C to obtain solution ①. At the same time, 100ml of dichloromethane, 20.4g of N-methylpyrrolidine, and 26ml of iodotrimethylsilane were added to a dry three-necked flask, and the temperature was kept at 20-25°C for 2 hours. Get the solution ②.

[0024] Mix solution ② and solution ① at 0-5°C, add 11ml of N,N-diethylaniline, react for 2h, after the reaction, add 20ml of methanol, 160ml of hydrochloric acid, 200ml of water, stir for 10 minutes, stand still, and separate The aqueous phase, the organic phase was extracted with water, and the aqueous phases were combined. Add 400ml of acetone to the water phase under stirring, adjust the pH to 2 with triethylam...

Embodiment 2

[0028] 1. Synthesis of 7-MPCA

[0029] In a 500ml round bottom flask, add 40g of 7-ACA, 27.4g of hexamethyldisilazane, and 200ml of cyclohexane in sequence, reflux at 85°C for 6h, then cool for later use. Add 50ml of cyclohexane, 35ml of N-methylpyrrolidine, and 26ml of iodotrimethylsilane into an anhydrous 250ml round-bottomed flask and react at reflux at 70°C for 3h, then cool for later use. Put the above two together into a 1000ml round bottom flask, cool to 0°C and quickly add 10ml of N,N-diethylaniline, after half an hour of reaction at 0°C, add 50ml isopropanol, 350ml water and 150ml concentrated hydrochloric acid dropwise until the solid dissolves. After liquid separation, the organic phase was re-extracted with 200 ml of water, the aqueous phases were combined, acetone was added dropwise to crystallize, and 40.2 g of the product was obtained by suction filtration and drying, with a yield of 82.3%.

[0030] 2, the synthesis of cefepime hydrochloride

[0031] Add 200m...

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Abstract

The invention relates to a method for synthesizing cefepime hydrochloride. The method comprises the following steps: taking 7-aminoce-phalosporanic acid (7-ACA) and N-methylpyrrolidine as raw materials, firstly, carrying out carboxylic and amino protection on the 7-ACA by HMDS, then preparing the N-methylpyrrolidine and iodotrimethylsilane into a quaternary ammonium salt intermediate, finally, adding the intermediate into the protected 7-ACA solution and reacting to prepare 7-MPCA; taking the 7-MPCA and AE-active ester, adding a phase transfer catalyst into an organic phase for carrying out an N-acidylating reaction, salifying and reacting to obtain the cefepime hydrochloride. The invention has the main characteristics that the quaternary ammonium salt intermediate is prepared in the step (1), the defects of high electron cloud density, strong reactivity and many side reactions of the N atom of N-methyl pyrrole are overcome, the yield is enhanced by 7%, and the product purity is enhanced. During the N-acidylating reaction in the organic phase in the step (2), the phase transfer catalyst is added, so that the conversion rate of the reaction is enhanced by 5%, and the product yield is enhanced.

Description

technical field [0001] The invention relates to a method for synthesizing the antibiotic cefepime hydrochloride. Background technique [0002] Cefepime is a fourth-generation cephalosporin, which has a broader antibacterial spectrum than third-generation antibiotics, has enhanced activity against Gram-positive bacteria, and is more stable against β-lactamase. Its drug is highly water-soluble and can quickly penetrate the bacterial outer membrane and the microporous protein channel with negative electrons, so it has the ability to quickly diffuse to the bacterial site and maintain the high activity of the drug, which can directly affect the bacterial cell wall It has a good inhibitory effect on Gram-negative bacteria, Gram-positive bacteria and some antibiotic-resistant strains. It has played a good role in the clinical treatment of lower respiratory tract, skin and bone tissue, urinary system, gynecology and abdominal cavity infection caused by sensitive bacteria. [0003]...

Claims

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Application Information

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IPC IPC(8): C07D501/46C07D501/06B01J31/02A61P31/04
Inventor 周磊樊会芬吴张静方宇
Owner YIYUAN XINQUAN CHEM
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