A kind of preparation method of cefotaxime sodium

A technology of cefotaxime sodium and cefotaxime acid is applied in the field of preparation of antibacterial drug cefotaxime sodium, can solve problems such as unfavorable production, research and utilization, unprotected functional groups, easy oxidative degradation and the like, and achieves improvement of market competition Good strength and color grade, reducing the effect of degradation process

Active Publication Date: 2021-02-09
辽宁美亚制药有限公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In the above process, due to the unprotected active functional groups such as 7-ACA amino carboxyl group, it is easy to be oxidized and degraded during the reaction process, and the result of high impurities
Moreover, the color grade of the obtained product is relatively high, which is not conducive to subsequent production, research and utilization

Method used

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  • A kind of preparation method of cefotaxime sodium
  • A kind of preparation method of cefotaxime sodium
  • A kind of preparation method of cefotaxime sodium

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1-1

[0068]Add 500ml of chloroform, 20g of 7-aminocephalosporanic acid and 22g of HMDS at room temperature. Increase the temperature and reflux for 5-6.0hr, then lower the temperature to below 20°C and add 28g of AE-active ester for condensation for 12-15hr.

[0069]Then, 300 ml of 8% sodium bicarbonate aqueous solution was added for extraction, and 2 g of activated carbon was added to the water phase for decolorization for 20 minutes and filtered. The temperature of the filtrate was controlled below 30°C, 130ml of acetone and 65ml of n-butanol were added, and the dilute acid solution was added dropwise to adjust the pH to 2.8-3.0, and crystals were precipitated. After filtering, the filter cake is washed with pure water, drained and then washed with acetone, drained and dried to obtain a crude cefotaxime acid with a yield of 85%.

[0070]The purity of the high-pressure liquid phase is 99.6%, and the color is yellow-green ≤2#. (See attachedfigure 1 )

Embodiment 1-2

[0072]Add 300 ml of anhydrous methanol to the reactor, add 15 g of sodium acetate, and stir to dissolve. Then add 45 g of crude cefotaxime acid, stir to dissolve. Add 2g of activated carbon, decolorize for 20min, and filter. The filtrate was dripped with acetone until it became turbid. Cultivate crystals for 60 minutes. Then add dropwise acetone in the later stage, lower the temperature to 0-5°C, and grow the crystals for 60 minutes. Suction filtration and drying gave cefotaxime sodium with a yield of 87%.

[0073]The purity of the high-pressure liquid phase is 99.6%, and the color is yellow-green ≤2#. (See attachedfigure 2 )

Embodiment 2-1

[0075]Add 300ml of dichloromethane, 20g of 7-aminocephalosporanic acid and 35g of BSU at room temperature. Increase the temperature and reflux for 5-6.0hr, then lower the temperature to below 20°C and add 30g of AE-active ester for condensation for 12-15hr.

[0076]Then, 200ml of 6% sodium hydroxide aqueous solution was added for extraction, and 2g of activated carbon was added to the water phase for decolorization for 20 minutes and filtered. The temperature of the filtrate was controlled below 30°C, 130ml of tetrahydrofuran and 65ml of n-butanol were added, and a dilute acid solution was added dropwise to adjust the pH to 2.8-3.0, and crystals were precipitated. After filtering, the filter cake was washed with pure water, drained and then washed with tetrahydrofuran, drained and dried to obtain crude cefotaxime acid with a yield of 88%.

[0077]The purity of the high-pressure liquid phase is 99.6%, and the color is yellow-green ≤2#. (See attachedimage 3 )

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Abstract

The invention provides a preparation method of cefotaxime sodium, which is characterized in that: after protecting the active group of 7-aminocephalosporanic acid with a silylating agent, condensation reaction occurs with AE-active ester to generate cefotaxime containing protective group Xamic acid; the cefotaxime acid containing the protective group is deprotected by the deprotection agent, followed by acidification and crystallization in the aqueous phase to obtain cefotaxime acid; the cefotaxime acid is obtained after salt formation and solvent crystallization Pure sodium oxime. The entire process reduces the degradation process of the product, significantly improves the product quality, improves the market competitiveness of the product, and further guarantees the safety of medication.

Description

Technical field[0001]The invention relates to the field of organic synthesis, in particular to a preparation method of antibacterial drug cefotaxime sodium.Background technique[0002]The chemical name of cefotaxime sodium is (6R,7R)-3-[(acetoxy)methyl]-7-[(2-amino-4-thiazolyl)-(methoxyimino)acetamido] Sodium -8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate. It is the third-generation cephalosporin antibiotic product for injection.[0003]At present, the technology of this variety is mainly 7-aminocephalosporan acid and 2-methoxyimino-2-(2-amino-4-thiazolyl)-(z)-thioacetate phenylhydrazine thiazole ester in dichloromethane or 2 -Add cefotaxime acid to a solvent such as methyl tetrahydrofuran, then add solvents such as organic alcohol, dropwise add dilute acid to adjust the pH crystallization, and centrifuge to obtain a completely dried cefotaxime acid solid.[0004]Then, the dried pure solid product is converted into sodium salt in an aqueous solution containing sodium acetate or ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D501/34C07D501/04C07D501/12
CPCC07D501/04C07D501/12C07D501/34Y02P20/55
Inventor 于永宏侯微王凤一
Owner 辽宁美亚制药有限公司
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