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Preparation method of cefmetazole sodium

The technology of cefmetazole sodium and cefmetazole benzil is applied in the field of preparation of cephalosporins in drug synthesis technology, and can solve the problems of low production yield of cefmetazole sodium crude drug, increased production cost, increased production steps and the like, Achieve the effect of not easy to degrade, improve yield and improve product quality

Inactive Publication Date: 2012-10-10
刘伟娜
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Chinese patent 201010100852.X discloses a method for refining cefmetazole sodium. The compound of cefmetazole sodium undergoes acid-base reaction, macroporous adsorption resin and activated carbon adsorption to achieve the purpose of purification, which increases the production steps and leads to a decrease in the total yield. , after the macroporous adsorption resin adsorbs cefmetazole, it is eluted with a large amount of solvent, and the post-treatment is complicated, which greatly increases the production cost
[0006] At present, the production yield of cefmetazole sodium bulk drug is low, the purity is not high, the production process is complicated, and the solvent consumption is large. Therefore, it is necessary to find a simple, easy, high yield, and good quality preparation method

Method used

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  • Preparation method of cefmetazole sodium
  • Preparation method of cefmetazole sodium

Examples

Experimental program
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Effect test

Embodiment 1

[0048] (1) preparation of cefmetazole benzyl axetil:

[0049] a. Add 40g of PCL5 to 400ml of dichloromethane, cool down to -1°C, add 40g of potassium cyanomethylthioglycolate, and stir at 8°C for 1 hour to prepare a cyanomethylthioglycol chloride solution for later use.

[0050] b. Add 133g of 7-MAC (alias methoxycephalosporin) to 665ml of dichloromethane, cool down to -50°C, add 66.5g of pyridine, dropwise add the cyanomethylmercaptoacetyl chloride solution in a, react at -40°C for 1h. Add 1330ml of 3% (W / V) dilute hydrochloric acid, stir, wash and separate the phases, discard the aqueous phase, add 1330ml of 5% (W / V) NaCl to the organic phase, stir, wash and separate the phases, discard the aqueous phase, and get methazole benzyl Ester dichloromethane solution for later use.

[0051] (2) Preparation of Cefmetazolamide Salt

[0052] a. Stir and cool down 376.83g of anisole to -10°C, and slowly add an anisole solution made of 113.05g of aluminum trichloride under stirring fo...

Embodiment 2

[0057] (1) preparation of cefmetazole benzyl axetil

[0058] a. Add 60 g of PCL5 to 300 ml of dichloromethane, cool down to -3°C, add 60 g of potassium cyanomethylthioglycolate, and stir at a temperature of 12°C for 1.5 hours to prepare a cyanomethylthioglycol chloride solution for later use.

[0059] b. Add 120g of 7-MAC to 1200ml of dichloromethane, cool down to -10°C, add 120g of triethylamine, dropwise add cyanomethylmercaptoacetyl chloride solution, react at -30°C for 2h. Add 600ml of 10% (W / V) hydrochloric acid, stir, wash and separate the phases, discard the aqueous phase, add 600ml of 10% (W / V) NaCl to the organic phase, stir, wash and separate the phases, discard the aqueous phase to obtain methazole benzyl ester di Chloromethane solution for later use.

[0060] (2) Preparation of Cefmetazolamide Salt

[0061] a. Stir and cool down 211.2g of anisole to 10°C, and slowly add an anisole solution made of 105.6g of aluminum trichloride under stirring for later use.

[0...

Embodiment 3

[0066] (1) preparation of cefmetazole benzyl axetil

[0067] a. Add 84g of PCL5 to 588ml of dichloromethane, cool down to -4°C, add 56g of potassium cyanomethylthioglycolate, and stir at a temperature of 10°C for 1.2h to prepare a cyanomethylthioglycol chloride solution for later use.

[0068] b. Add 80g of 7-MAC (alias methoxycephalosporin) to 600ml of dichloromethane, cool down to -30°C, add 50g of pyridine, dropwise add cyanomethylmercaptoacetyl chloride solution, react at -35°C for 1.5h, add 560ml of 8-MAC % (W / V) hydrochloric acid stirring and washing phase separation, discarding the aqueous phase, adding 640ml of 8% (W / V) NaCl to the organic phase, stirring, washing and separating the phases, discarding the aqueous phase to obtain a methazole benzyl ester dichloromethane solution for subsequent use .

[0069] (2) Preparation of Cefmetazolamide Salt

[0070] a. Stir and cool down 172g of anisole to 0°C, slowly add anisole solution made of 68.8g of aluminum trichloride u...

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Abstract

The invention discloses a preparation method of cefmetazole sodium, comprising the following steps: (1) dissolving phosphorus pentachloride in dichloromethane, then adding cyanomethylthio potassium acetate to prepare a side-chain acyl chloride solution; dissolving 7-MAC in dichloromethane, and adding organic base and the above side-chain acyl chloride solution to wash to obtain a cefmetazole benzyl ester solution; (2) adding the cefmetazole benzyl ester solution in an aluminum trichloride anisole solution, washing, regulating the pH value to 6.0-9.0, crystallizing, filtering and drying to obtain cefmetazole amine salt; and (3) dissolving the cefmetazole amine salt in an organic solvent solution, adding cation exchange resin, removing the cation exchange resin by filtration, regulating the pH to 5-8, then removing the organic solvent by distillation at reduced pressure, letting the residual cefmetazole sodium solution be subject to decoloration and aseptic filtration, and then directly conducting freeze-drying to obtain cefmetazole sodium. The method is simple and practicable and has the advantages of high yield, good quality and low cost.

Description

Technical field: [0001] The invention relates to a preparation method of cefmetazole sodium, which belongs to the field of preparation of cephalosporin compounds in the pharmaceutical synthesis technology. Background technique: [0002] Cefmetazole sodium, its English name is Cefmetazole sodium, its chemical name is: (6R, 7S)-7-[[2-(cyanomethylthio)acetyl]amino]-7-methoxy-3-[(1 -Methyltetrazol-5-yl)thiomethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid sodium salt, molecular formula: C15H16N7NaO5S3, Molecular weight: 493.52, structural formula: [0003] [0004] Cefmetazole sodium is a second-generation cephalosporin, which has good stability to the broad-spectrum-lactamase produced by negative bacilli, such as Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Shigella, Salmonella Streptococcus aureus, group A hemolytic streptococcus and catabraham bacteria are highly sensitive to this product, and have good antibacterial activity against Bact...

Claims

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Application Information

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IPC IPC(8): C07D501/57C07D501/04
Inventor 刘伟娜
Owner 刘伟娜
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