A kind of preparation method of cephamycin intermediate

An intermediate, cephamycin technology, which is applied in the field of pharmaceutical chemical synthesis, can solve the problems of complex steps and large recycling pollution, and achieve the effects of reducing costs, less pollution, and improving product yields

Active Publication Date: 2018-01-12
山东安弘制药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] Aiming at the shortcomings of the synthesis process of cephamycin intermediates in the prior art, such as solvents such as boron trifluoride acetonitrile, which are difficult to recycle, pollute, and have complicated steps, the present invention provides a cephamycin intermediate with simple operation, low pollution and low cost. The preparation method of body, this method is suitable for industrialized production application

Method used

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  • A kind of preparation method of cephamycin intermediate
  • A kind of preparation method of cephamycin intermediate
  • A kind of preparation method of cephamycin intermediate

Examples

Experimental program
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Effect test

Embodiment 1

[0041] A preparation method of cephamycin intermediate shown in formula (IV), comprising the steps of:

[0042] (1) Add 10g of 7-ACA raw material into 100ml of water, then add 9.25g of sodium bicarbonate, stir at 30-35°C for 1-2h to dissolve, cool down to 0-5°C, and add 8.14g of dichloroethylene dropwise under temperature control Acyl chloride, keep stirring and reacting at 0-5°C for 30 minutes, adjust the pH to 4.5-5.0 with 30wt% sodium hydroxide, crystallize in large quantities, grow crystals at 0-5°C for 2 hours, filter, wash the filter cake with 15ml water, and the product is 25-5 Dry at 30°C to obtain 13.2 g of the compound of formula (II), the product purity is greater than 98%, and the molar yield: 93.6%.

[0043] (2) Add 3.0g MMT to 100ml ethyl acetate, stir at 10-25°C for 30min to dissolve, add 8.8g of the compound of formula (II) prepared in step (1), then add 0.5g of solid sulfonic acid catalyst PEP-14, heat Heat the reaction at 50°C for 3.5 hours, recover the soli...

Embodiment 2

[0046] Preparation method as described in Example 1, the difference is that,

[0047] Step (1) Add 10g of 7-ACA to 50ml of 30wt% formic acid solution, stir at 20-25°C for 60min to dissolve, cool the feed liquid to 0-5°C, add 8.14g of dichloroacetyl chloride dropwise, and control the temperature at 0-5 Stir and react at ℃ for 30 minutes, adjust the pH to about 4.5-5.0 with 30wt% sodium hydroxide, crystallize in large quantities, grow crystals at 0-5℃ for 2 hours, filter, wash the filter cake with 15ml water, and dry the product in vacuum to obtain compound 8.8 of formula (II) g, purity 93.5%, molar yield: 70.91%.

Embodiment 3

[0049] Preparation method as described in Example 1, the difference is that,

[0050] Ethyl acetate in the step (2) is changed into acetone;

[0051] Finally, 10.5 g of DCT in the form of triethylamine (compound represented by formula (IV)) was obtained, with a purity of 98.2% and a molar yield of 84.6%.

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Abstract

The invention relates to a preparation method of a cephamycin intermediate. The cephamycin intermediate compound has a structure of formula (IV), and is prepared by reacting 7‑ACA with dichloroacetyl chloride in a specific solvent, reacting the obtained product with MMT under the catalysis of a sulfonic acid catalyst, and crystallizing. The cephamycin intermediate of the present invention has the characteristics of high purity and good stability, and is beneficial to improving the purity of cefamycin final products such as cefminox sodium, cefmetazole sodium and cefotetan disodium, and is beneficial to large-scale production and application .

Description

technical field [0001] The invention relates to a preparation method of a cephamycin intermediate DCT, which belongs to the technical field of pharmaceutical chemical synthesis. Background technique [0002] Cephamycin antibiotics are clinically commonly used drugs for the treatment of diseases caused by bacterial infections. Due to the presence of methoxy at the 7α-position in the mother nucleus, they are highly stable to β-lactamase and belong to enzyme-resistant antibiotics. [0003] Synthesis of 7β-chloroacetamide-7α-methoxy-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid as cephamycins The key intermediate of DCT, referred to as DCT. At present, the common cephalosporins in the global market include cefminox sodium, cefmetazole sodium, cefotetan disodium and cefoxitin sodium. [0004] Chinese patent document CN102268021A provides a kind of preparation method of cefminox sodium, this method first with 7-ACA (3-acetoxymethyl-5-sulfur-7-amino-8-oxo-1-a...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D501/57C07D501/04
CPCY02P20/584
Inventor 姚甲玉赵卫良符淙淙冯宪东
Owner 山东安弘制药有限公司
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