Method for synthesizing cefuroxime acid

A technology of cefuroxime acid and mixed solution, applied in the direction of organic chemistry, etc., can solve the problems of increasing the cost of cefuroxime acid, harming human health, high processing cost, etc., and achieves low solvent recovery cost, reduced production cost, and shortened operation period Effect

Inactive Publication Date: 2014-10-01
珠海保税区丽珠合成制药有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] Chinese patent CN101289456A then reports that in a solvent system such as dimethyl carbonate, the nucleophilic addition reaction of 3-deformylamino cefuroxime acid (DDC) and chlorosulfonic acid isocyanate is used to generate chlorosulfonylated cefuroxime acid , add purified water to hydrolyze to obtain cefuroxime acid, then add dichloromethane, and crystallize at low temperature to obtain cefuroxime acid, the resulting yield is as low as 88.23%, and the product purity is only 98.11%
[0013] However, in the synthetic routes reported by the above-mentioned patent process, either a more toxic reaction solvent is used, which is seriously harmful to human health, such as tetrahydrofuran; or a ternary mixed system is used, such as tetrahydrofuran, dichloromethane and acetic acid Ethyl ester, etc., resulting in high post-processing costs, thereby increasing the cost of producing cefuroxime acid

Method used

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  • Method for synthesizing cefuroxime acid
  • Method for synthesizing cefuroxime acid
  • Method for synthesizing cefuroxime acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Add ethyl acetate (500ml), DDC (50g, 117.82mmol) to a 1000ml three-necked flask in sequence, then control the temperature T1 = 5-10°C, and drop 15mL of CSI in 10 minutes. Control temperature T2=15-20°C, add 2.5g of activated carbon, stir and react for 30min, then filter. The filtrate was cooled to about 5°C, then 70mL of purified water was added dropwise for 5min, followed by NaHCO3 solution (53gNaHCO 3 + 284mL water), dripped in 30min. The liquid was separated, the ethyl acetate layer was discarded, and 30% HCl was added dropwise to adjust the pH value, and the temperature was lowered to T3=0-5° C. to grow crystals for 1 h. Suction filtration, wash the filter cake twice with water, 50 mL each time, drain it, and dry it in vacuum at 50°C for 3 hours. The reaction products are shown in Table 1:

[0034] Table 1. The influence of different pH values ​​on the reaction products

[0035]

[0036] Conclusion: From Table 1, it can be found that when the pH value is 1-4, ...

Embodiment 2

[0038] Add ethyl acetate (500ml) and DDC (50g, 117.82mmol) to a 1000ml three-necked flask in sequence, then control the temperature T1 = 0-5°C, and drop 15mL of CSI in 10 minutes. Control temperature T2=15-20°C, add 2.5g of activated carbon, stir and react for 30min, then filter. Cool the filtrate to about 5°C, then add 70 mL of purified water dropwise for 5 minutes, then add NaHCO dropwise 3 Solution (53gNaHCO 3 + 284mL water), dripped in 30min. The liquid was separated, the ethyl acetate layer was discarded, 30% HCl was added dropwise, the pH was adjusted to 2.0, and the temperature was lowered to T3=0-5°C to grow crystals for 1 h. After suction filtration, the filter cake was washed twice with 50 mL of water each time, sucked dry, and dried in vacuum at 50° C. for 3 hours to obtain 50.8 g of a white solid product with a moisture content of 0.18%, an HPLC purity of 99.25%, and a molar yield of 91.30%.

Embodiment 3

[0040] Add ethyl acetate (500ml) and DDC (50g, 117.82mmol) to a 1000ml three-necked flask in sequence, then control the temperature T1 = 10-15°C, and drop 15mL of CSI in 10 minutes. Control temperature T2=15-20°C, add 2.5g of activated carbon, stir and react for 30min, then filter. Cool the filtrate to about 5°C, then add 70 mL of purified water dropwise for 5 minutes, then add NaHCO dropwise 3 Solution (53gNaHCO 3+ 284mL water), dripped in 30min. The liquid was separated, the ethyl acetate layer was discarded, 30% HCl was added dropwise, the pH was adjusted to 2.0, and the temperature was lowered to T3=0-5°C to grow crystals for 1 h. After suction filtration, the filter cake was washed twice with 50 mL of water each time, sucked dry, and dried in vacuum at 50° C. for 3 h to obtain 49.5 g of a white solid product with a moisture content of 0.16%, an HPLC purity of 99.00%, and a molar yield of 88.96%.

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Abstract

The invention relates to a preparation method for synthesizing cefuroxime acid, which comprises the following steps: A) dropwisely adding isocyanate chlorosulfonate into a mixed solution of ethyl acetate and 3-decarbamoyl-cefuroxime acid at 0-15 temperature; B) while controlling the temperature at 15-25 DEG C, continuing adding activated carbon into the reaction solution, stirring to react, and filtering; and C) taking the filtrate, cooling, adding water, continuously adding sodium bicarbonate, skimming, discarding the ethyl acetate layer, dropwisely adding 30% HCl to regulate the pH value, cooling to 0-10 below, growing the grain, carrying out vacuum filtration, and washing the filter cake with water.

Description

technical field [0001] The invention relates to the field of medicine preparation, in particular to a preparation method of cefuroxime acid. Background technique [0002] Cefuroxime acid (Cefuroxim, structural formula 1), (6R,7R)-7-[2-furyl(methoxyimino)acetamido]-3-carbamoyloxymethyl-8-oxo-5-sulfur Hetero-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid. [0003] Structural Formula 1 (Cefuroxime Acid): [0004] [0005] Cefuroxime is a cephalosporin antibiotic developed by the British Glaxo Company. It belongs to the second-generation cephalosporin and has a broad-spectrum antibacterial effect. It not only has strong antibacterial activity against Gram-positive cocci, but also has Gram-negative bacteria also have good antibacterial activity, especially in the treatment of mixed infections of Gram-positive and Gram-negative bacteria, this drug is preferred. It has high stability to the hydrolytic enzyme produced by bacteria that destroys the drug effect, and rarely cause...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D501/04C07D501/34
CPCC07D501/04C07D501/34
Inventor 王建军张鹏贾晓伟李显焕明建李波肖鸿
Owner 珠海保税区丽珠合成制药有限公司
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