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One-pot synthesis method of ceftriaxone sodium

A technology of ceftriaxone sodium and a synthesis method, which is applied in the field of medicinal chemical synthesis, can solve the problems of drug contamination, physical injury of operators, troublesome operation, etc., and achieves the effects of avoiding potential pollution, simplifying production operations, and increasing production costs.

Inactive Publication Date: 2015-11-18
山东安弘制药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are following disadvantages in the above synthesis process, 1) solvent toxicity is large, troublesome operation, high cost, unfavorable for continuity, large-scale industrial production; It is easy to cause allergic and other adverse reactions
3) Due to the existence of the intermediate 7-ACT, the chances of operators to contact raw materials and intermediates increase, the probability of drug contamination increases, and the probability of operators being allergic due to long-term contact will also increase, which is harmful to the operator's body. cause some damage

Method used

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  • One-pot synthesis method of ceftriaxone sodium
  • One-pot synthesis method of ceftriaxone sodium
  • One-pot synthesis method of ceftriaxone sodium

Examples

Experimental program
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Effect test

Embodiment 1

[0050] (1) Control the temperature at 20-25°C, put 35g of boron trifluoride ethyl acetate complex into 150ml of ethyl acetate, stir until it is completely dissolved, add 15g of triazine ring, 25g of 7-ACA, and control the temperature at 30°C for timing React for 20 minutes, add 120ml of water after the reaction, immediately lower the temperature to 5°C, stir, let stand to separate layers, and wash the organic phase twice with 120ml of water to obtain the ethyl acetate phase of 7-ACT;

[0051] (2) Add 100ml of dichloromethane, 30ml of methanol, 1ml of sulfurous acid, and 15ml of water to the ethyl acetate phase of 7-ACT in sequence, then add 31g of AE active ester, control the temperature at 2°C, and add 25ml of triethylamine dropwise for 45min After the internal dropwise addition is completed, keep warm until the reaction solution residue is detected to be qualified, add 23g of sodium acetate and 100g of purified water for salt formation and extraction, stand for stratification...

Embodiment 2

[0053] (1) Control the temperature at 20-25°C, put 35g of boron trifluoride ethyl acetate complex into 150ml of ethyl acetate, stir until it is completely dissolved, add 15g of triazine ring, 25g of 7-ACA, and control the temperature at 30°C for timing React for 20 minutes, add 120ml of water after the reaction, immediately lower the temperature to 6°C, stir, let stand to separate layers, and wash the organic phase twice with 120ml of water to obtain the ethyl acetate phase of 7-ACT;

[0054] (2) Add 100ml of dichloromethane, 30ml of ethanol, 0.35g of sodium metabisulfite, 15ml of water to the ethyl acetate phase of 7-ACT, then add 31g of AE active ester, control the temperature at 1°C, and add 18.5ml of diethylamine dropwise , the dropwise addition is completed within 60 minutes, keep warm until the residual of the reaction solution is qualified, add 23g of sodium acetate and 100g of purified water for salt formation and extraction, stand for stratification, decolorize and fil...

Embodiment 3

[0056] (1) Control the temperature at 20-25°C, put 35g of boron trifluoride ethyl acetate complex into 150ml of ethyl acetate, stir until completely dissolved, add 15g of triazine ring, 25g of 7-ACA, and control the temperature at 28°C for timing React for 20 minutes, add 120ml of water after the reaction, immediately lower the temperature to 8°C, stir, let stand to separate layers, and wash the organic phase twice with 120ml of water to obtain the ethyl acetate phase of 7-ACT;

[0057] (2) Add 100ml of dichloromethane, 30ml of isopropanol, 0.30g of sodium thiosulfate, and 15ml of water to the ethyl acetate phase of 7-ACT in sequence, then add 31g of AE active ester, control the temperature at 3°C, and drop 22.5 ml of tetramethylguanidine, the dropwise addition is completed within 60 minutes, keep the reaction until the residual of the reaction solution is qualified, add 14g of sodium bicarbonate and 100g of purified water for salt formation and extraction, stand for stratifica...

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Abstract

The invention relates to a one-pot synthesis method of ceftriaxone sodium. The adopted one-pot synthesis method comprises the following steps: directly adopting an organic solution of 7-ACT as the intermediate 7-ACT is not separated in a solid manner, adding an organic solvent B, an antioxidant and water into the organic solution of the 7-ACT, then, adding AE active ester, performing further reaction under the action of organic base, adding a salt forming agent for salt formation, performing standing, extraction, water phase decolorization and filtering, and adding water-soluble organic solvent C crystal, so as to obtain the ceftriaxone sodium. According to the method for synthesizing the ceftriaxone sodium, the whole-process non-artificial direct contact to materials can be realized, the whole-process whole-solvent flow-state closed operation can be implemented, the control on the interaction effect of personnel and materials during the production process is facilitated, the shortening of the production period is facilitated, the production operation is simplified, the discharge of waste liquid is reduced, the energy consumption during the intermediate drying process is reduced, and the effect of reducing the cost to a certain degree is achieved.

Description

technical field [0001] The invention relates to a one-pot synthesis method of ceftriaxone sodium, belonging to the technical field of pharmaceutical chemical synthesis. Background technique [0002] Ceftriaxone sodium, also known as ceftriaxone, chemical name is (6R,7R)-7-[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-8-oxo- 3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl)thio]methyl]-5 - Thio-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid disodium salt triple hemihydrate, the molecular formula is: C 18 h 16 N 8 Na 2 o 7 S 3 ·31 / 2H 2 O; molecular weight: 661.59, structural formula: [0003] [0004] Ceftriaxone sodium was successfully developed in 1978 by Refiner, a Swiss Roche company chemist. It was first listed in Switzerland in 1982, and it was certified by FDA on December 21, 1984. After its patent expired in 1996, ceftriaxone sodium began to have amazing The speed of growth in our country. At present, ceftriaxone sodium is one of the 22 k...

Claims

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Application Information

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IPC IPC(8): C07D501/36C07D501/06
CPCC07D501/36C07D501/06
Inventor 赵卫良刘月谢鹏符淙淙赵丹丹
Owner 山东安弘制药有限公司
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