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Preparation method of cefamandole nafate

A technology for cefmandole sodium and cefene, which is applied in the field of preparation of cefmandole sodium, can solve the problems of complicated process operation, influence on product yield and final product quality, etc., and achieves simple operation process, low cost and simple cost Effect

Active Publication Date: 2010-11-10
HAINAN HULUWA PHARMA GRP CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The method is complex in process operation, and silamine easily produces by-product ammonia, which affects the yield of the product and the quality of the final product

Method used

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  • Preparation method of cefamandole nafate
  • Preparation method of cefamandole nafate

Examples

Experimental program
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Effect test

Embodiment 1

[0035] Preparation of 7-D-(2-formyloxyphenylacetamide)-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-3-cephem-4-carboxylic acid

[0036]Suspend 258g (0.798mol) of 7-amino-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-3-cephem-4-carboxylic acid and 375g of sodium bicarbonate in Add 1000ml of acetone solution containing 148.8g (0.75mol) of α-formylmandelic acid chloride to a mixture of 7500ml of water and 7500mL of acetone that has been precooled to 5°C, keep stirring at 5°C for 1 hour, then heat up Continue to stir and react at 20°C for 2 hours. After the reaction is over, distill off the acetone at 20°C under reduced pressure, add ethyl acetate to the raffinate for extraction, and extract twice. The amount of ethyl acetate each time is 6L, and the two extractions are combined. liquid, dried over anhydrous sodium sulfate, concentrated under reduced pressure at 20°C to dryness to obtain a light yellow oil; recrystallized the light yellow oil with ether to obtain 383 g of a light yellow ...

Embodiment 2

[0040] 7-D-(2-formyloxyphenylacetamide)-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-3-cephem-4-carboxylic acid sodium salt preparation

[0041] Dissolve 383 g of the light yellow powder obtained in Example 1 in 1.5 L of acetone, then add 1.2 L of acetone solution containing 92 g (0.55 mol) of sodium isooctanoate, cool to 0° C. in an ice bath, continue stirring for 3 hours, filter, The filter cake was washed with acetone and dried under reduced pressure at 40°C for 5 hours to obtain 276.2 g of crude product with a melting point (mp) of 183°C-185°C. The molar yield was 93.8%.

[0042] The above-mentioned crude product is carried out elemental analysis, the result is as follows: C: 44.7%, H: 3.5%, N: 16.3%, O: 18.6%, S: 12.5%, Na: 4.4% (all are mass percent), and 7- Theoretical value of D-(2-formyloxyphenylacetamide)-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-3-cephem-4-carboxylic acid sodium salt : C: 44.5%, H: 3.4%, N: 16.4%, O: 18.7%, S: 12.5%, Na: 4.5% (both mass percentages)...

Embodiment 3

[0045] Preparation of Refined Product of Cefamandole Sodium

[0046] The 276.2g crude product obtained in Example 2 was dissolved in 5000ml of anhydrous methanol, 10g of gac was added under stirring, stirred and decolorized for 30 minutes, filtered to obtain the filtrate, the filtrate was slowly added to 15000ml of ethyl acetate, at room temperature Continue to stir and crystallize for 4 hours, filter, wash the filter cake with a mixed solution of anhydrous methanol and ethyl acetate (the volume ratio of anhydrous methanol to ethyl acetate is 1:1), collect the filter cake, and dry under vacuum at 40°C to obtain The refined product of cefamandole sodium is 256.3g, the yield is 92.8%, and the mp of the refined product of cefamandole sodium is 189°C-190.5°C.

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Abstract

The invention discloses a preparation method of cefamandole nafate, which comprises the following steps: (1) suspending 7-amino-3-[(1-methyl-1H-tetrazol-5-yl) S-methyl] -3-cephem-4-carboxylic acid and sodium bicarbonate in an acetone water solution, adding the acetone solution of alpha-formylmandeloyl chloride to carry out a condensation reaction, and preparing 7-D-(2-formyloxy phenylacetamide)-3- [(1-methyl-1H-tetrazol-5-yl) S-methyl]-3-cephem-4-carboxylic acid; and (2) dissolving the 7-D-(2-formyloxy phenylacetamide)-3- [(1-methyl-1H-tetrazol-5-yl) S-methyl]-3-cephem-4-carboxylic acid in acetone to carry out a salification reaction with the acetone solution of organic acid sodium to prepare the cefamandole nafate. The method has the advantages of simple technology, high product yield, high purity, high reaction selectivity and use of no special equipment in production, and is suitable for industrialized production.

Description

technical field [0001] The invention relates to the field of raw material medicine preparation, in particular to a preparation method of cefamandole sodium. Background technique [0002] Cefamandole sodium, chemical name: 7-D-(2-formyloxyphenylacetamido)-8-oxo-3-[(1-methyl-1H-tetrazol-5-yl)sulfur Methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid sodium salt or 7-D-(2-formyloxyphenylacetamide)-3-[(1 -Methyl-1H-tetrazol-5-yl)thiomethyl]-3-cephem-4-carboxylic acid sodium salt, molecular formula: C 19 h 17 N 6 NaO 6 S 2 , Molecular weight: 512.50, CAS number: 42540-40-9, the chemical structure is as follows: [0003] [0004] At present, there are many cefamandole sodium preparations. For example, the injection of sporin derivatives developed by Eli Lilly Company of the United States: cefamandole sodium for injection. In September 1983, Shionogi Pharmaceutical Co., Ltd. obtained the approval of cefdoxazole sodium preparation with the trade name kefdole in ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D501/36C07D501/06
Inventor 刘全国
Owner HAINAN HULUWA PHARMA GRP CO LTD
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