Method for synthesizing cephalosporin intermediate

A synthesis method and intermediate technology are applied in the field of synthesis of cephalosporin intermediates, can solve the problem that the synthesis method of cephalosporin intermediates is not suitable for industrial production, etc., and achieve the effects of good solubility, convenient operation and mild reaction conditions

Active Publication Date: 2010-07-07
SHANGHAI NEW ASIA PHARMA
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0009] The technical problem to be solved by the present invention is to provide a synthetic method of 7-ATCA HCl for the problem that the existing cephalosporin intermediate synthetic method is not suitable for industrial production. The method is easy to operate, suitable for industrial production, and has high yield. The 7-ATCA·HCl produced has high purity

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  • Method for synthesizing cephalosporin intermediate
  • Method for synthesizing cephalosporin intermediate

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Embodiment 1

[0029] In the present embodiment, a kind of synthetic method of cephalosporin intermediate adopts the following steps:

[0030] 1. Add 100ml of acetonitrile to a 500ml three-necked flask, add 10g of 1-methyl-5-mercaptotetrazolium into the acetonitrile, and add 20g of 7-aminocephalosporanic acid while stirring; the reaction solution is heated to 50 ℃, add 110ml boron trifluoride acetonitrile solution with 20% boron trifluoride content, keep stirring at this temperature for 2h.

[0031] 2. After the reaction is over, cool the reaction solution to room temperature, add 3 g of activated carbon, and stir for 15 minutes. Filter, wash the charcoal with 150 ml of acetone aqueous solution (V acetone / V water=1 / 1) containing 0.5% hydrochloric acid, and the washing liquid is combined with the filtrate.

[0032] 3. Add the combined filtrate to 100ml acetone aqueous solution (V acetone / V water=1 / 1), stir, slowly add 8% sodium bicarbonate solution dropwise until the pH value of the solution...

Embodiment 2

[0036] In the present embodiment, a kind of synthetic method of cephalosporin intermediate adopts the following steps:

[0037] 1. Add 100ml of acetonitrile to a 500ml three-necked flask, add 10g of 1-methyl-5-mercaptotetrazolium into the acetonitrile, and add 20g of 7-aminocephalosporanic acid while stirring; the reaction solution is heated to 25 ℃, add 35ml of boron trifluoride ether solution with boron trifluoride content of 47%, and keep stirring at this temperature for 1 h.

[0038] 2. After the reaction is finished, cool the reaction solution to room temperature, add 3 g of activated carbon to the solution, and stir for 30 minutes. Filter, wash the charcoal with 25 ml of acetone aqueous solution containing 5% hydrochloric acid (V acetone / V water=1 / 4), and the washing liquid is combined with the filtrate.

[0039] Three, the combined filtrate is added in 200ml acetone aqueous solution (V acetone / V water=1 / 4), stir, slowly add dropwise 10% sodium carbonate solution to sol...

Embodiment 3

[0043] In the present embodiment, a kind of synthetic method of cephalosporin intermediate adopts the following steps:

[0044] 1. Add 250ml of acetonitrile into a 1000ml three-necked flask, add 15g of 1-methyl-5-mercaptotetrazolium into the acetonitrile, add 29g of 7-aminocephalosporanic acid while stirring, and heat the reaction solution to 35°C , add 40ml of boron trifluoride tetrahydrofuran solution with a boron trifluoride content of 47%, keep the temperature and stir for 2h;

[0045]2. After the reaction, cool the reaction solution to room temperature, add 5 g of activated carbon, stir for 20 min, and filter; wash the carbon with 20 ml of acetone aqueous solution (V acetone / V water=4 / 1) containing 10% hydrochloric acid, and the washing liquid and the filtrate are combined .

[0046] 3. Add the combined filtrate to 120ml acetone aqueous solution (V acetone / V water=4 / 1), stir, slowly add 15% sodium hydroxide solution dropwise until the pH value of the solution is 2.0, sto...

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Abstract

The invention discloses a method for synthesizing a cephalosporin intermediate, which comprises the following steps: 1, adding 1-methyl-5-mercaptotetrazole and 7-amino-cephalosporanic acid into acetonitrile with stirring, heating the solution, and adding a boron trifluoride complex compound into the solution; 2, adding a proper amount of active carbon into the solution, stirring and filtering thesolution, washing the carbon by using aqueous solution of acetone containing hydrochloric acid, and merging filtrate; 3, adding the merged filtrate into the aqueous solution of acetone, stirring the solution, slowly dripping alkali solution till the pH value of the solution is 2.0 to 3.5, and growing crystals for 1 to 2 hours; and 4, filtering the solution, transferring the filtrate to another container, reclaiming the acetonitrile and the acetone, washing the obtained crystals twice to trice by using the acetone, filtering the solution, and then drying the crystals under vacuum. Aiming at the problem that the conventional method for synthesizing the cephalosporin intermediate is not suitable for industrialized production, the invention provides the method for synthesizing the cephalosporin intermediate; the method is simple and convenient to operate, is suitable for industrialized production and has high yield; and the prepared 7-ATCA.HCl has high purity.

Description

technical field [0001] The invention relates to a synthetic method of a cephalosporin intermediate. Background technique [0002] 7-ATCA, the chemical name is 7-amino-3-[(1-methyl-tetrazol-5-yl)-thiomethyl]-ceph-3-ene-4-carboxylic acid, and its structural formula is as follows. [0003] [0004] 7-ATCA is an important intermediate for the preparation of semi-synthetic cephalosporin antibiotics, and can be used to synthesize another important cephalosporin intermediate 7-MAC as well as cefoperazone, cefpiramide, cefamandole, cefmenoxime, cefmetazole, and cefmetazole Minol, cefbuperazone, cefotetan and other drugs. The commonly used 7-ATCA is its hydrochloride salt form 7-ATCA.HCl. [0005] The synthesis of 7-ATCA·HCl can be 7-aminocephalosporanic acid (referred to as 7-ACA) as the starting material, and under the catalysis of the catalyst, it undergoes a condensation reaction with 1-methyl-5-mercaptotetrazolium (abbreviated as MMT). Then get salt. [0006] Chen Sheng e...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D501/18C07D501/36
Inventor 郑玉林管海英孙大钧王立新李晴
Owner SHANGHAI NEW ASIA PHARMA
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