Preparation method of sulbenicillin sodium

A technology of sulfbenicillin sodium and sulfophenylacetic acid, which is applied in the direction of organic chemistry, can solve the problems of difficulty in improving product quality, instability of sulfophenylacetyl chloride, incomplete reaction, etc., and achieve excellent product quality, suitable for industrial production, The effect of easy operation

Inactive Publication Date: 2013-05-22
FUAN PHARM (GRP) CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] The advantage of this route is that there are few steps, and the operation is relatively simple. The disadvantage is that sulfophenylacetyl chloride is unstable...

Method used

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  • Preparation method of sulbenicillin sodium
  • Preparation method of sulbenicillin sodium

Examples

Experimental program
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Effect test

Embodiment 1

[0030] Dissolve 216g (1mol) sulfophenylacetic acid in anhydrous 1000ml dichloromethane, add 202.4g (2.2mol) propionyl chloride, cool to 0-5°C, add dropwise 449.5g (4.45mol) triethylamine, after completion React at 25°C for 3 hours, transfer the reaction solution into a separatory funnel, wash with water, extract with dichloromethane, dry and concentrate to obtain mixed anhydrides.

[0031] Weigh 202.3g (0.85mol) 6-APA and 243.3g (1.19mol) N, N-bis(trimethylsilyl)-2,2,2-trifluoroacetamide in the reaction flask, and nitrogen For protection, inject 1200ml of ethyl acetate as a solvent, raise the temperature to about 50°C and stir for 2 hours, after the reaction is completed, cool down to room temperature, wash with water, extract with ethyl acetate, and then dry and concentrate.

[0032] Use ethanol as a solvent, cool down to 0-5°C, slowly add step (1) to obtain mixed anhydride and 6-APA protected by step (2), keep warm for 45 minutes, acidify with hydrochloric acid, raise to 25°...

Embodiment 2

[0034] Dissolve 216g (1mol) sulfophenylacetic acid in anhydrous 1100ml dichloromethane, add 222.6g (2.1mol) butyryl chloride, cool to 0-5°C, add dropwise 454.5g (4.5mol) triethylamine, after completion React at 30°C for 3 hours, transfer the reaction solution into a separatory funnel, wash with water, extract with dichloromethane, dry and concentrate to obtain mixed anhydrides.

[0035] Weigh 202.3 grams (0.85mol) of 6-APA and 259.4 grams (1.27mol) of N, O-bis(trimethylsilyl)acetamide and put it into a reaction flask, vacuumize it and inject it into 1200ml of ethyl acetate to make The solvent was heated to about 50°C and stirred for 2 hours. After the reaction was completed, it was lowered to room temperature, washed with water, extracted with ethyl acetate, dried and concentrated.

[0036] Use ethanol as solvent, cool down to 0-5°C, slowly add step (1) to obtain mixed anhydride and 6-APA protected by step (2), keep warm for 30 minutes, acidify with hydrochloric acid, raise to...

Embodiment 3

[0038] Dissolve 216g (1mol) sulfophenylacetic acid in anhydrous 1200ml dichloromethane, add 300g (2.5mol) pentanoyl chloride, cool to 0-5°C, add dropwise 454.5g (4.5mol) triethylamine, after completion React at 30°C for 3 hours, transfer the reaction solution into a separatory funnel, wash with water, extract with dichloromethane, dry and concentrate to obtain mixed anhydrides.

[0039] Weigh 202.3 g (0.85 mol) of 6-APA and 219.5 g (1.36 mol) of hexamethyldisilazane into a reaction bottle, vacuumize and protect with nitrogen, inject 1350 ml of ethyl acetate as a solvent, and heat up to about 55 °C After stirring for 2 hours, the reaction was completed, cooled to room temperature, washed with water, extracted with ethyl acetate, dried and concentrated.

[0040] Use ethanol as a solvent, cool down to 0-5°C, slowly add step (1) to obtain mixed anhydride and 6-APA protected by step (2), keep warm for 50 minutes, acidify with hydrochloric acid, raise to 30°C, add sodium isooctanoat...

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Abstract

The invention provides a preparation method of sulbenicillin sodium. The preparation method comprises the following steps: condensing sulfophenylacetic acid and acyl chloride to generate mixed anhydride, condensing the mixed anhydride and protected 6-APA under an anhydrous condition, de-protecting to obtain sulbenicillin acid, reacting the obtained sulbenicillin acid with sodium isooctoate to obtain a salt, and crystallizing to obtain sulbenicillin sodium having a purity of above 99.2%. The preparation method has the advantages of simple operation, mild conditions, high yield, low cost and the like, and is suitable for the industrialized production; and the preparation method simultaneously allows the discharge amounts of three wastes to be substantially reduced and the environmental pollution to be small.

Description

technical field [0001] The invention belongs to the technical field of medicine and chemical industry, and in particular relates to a preparation method of sulbenicillin sodium. Background technique [0002] Sulbenicillin sodium, the English name is Sulbenicillin Sodium, the Chinese chemical name is: (2S, 5R, 6R)-3,3-dimethyl-6-((R)-2-phenyl-2-sulfoacetamido )-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid disodium salt, the structural formula is as follows: [0003] [0004] Sulbenicillin sodium structural formula [0005] Sulbenicillin sodium is a broad-spectrum semi-synthetic penicillin antibiotic. Its antibacterial spectrum is similar to carbenicillin. It binds to the penicillin-binding protein on the cell membrane to hinder the synthesis of bacterial cell wall mucopeptides, making it impossible to cross-link and cause cell wall damage. cause bacterial cell rupture and death. It is mainly suitable for pneumonia, urinary tract infection, complicated skin ...

Claims

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Application Information

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IPC IPC(8): C07D499/62C07D499/16
Inventor 周旭东洪荣川郭子维蒋晨
Owner FUAN PHARM (GRP) CO LTD
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