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Method for synthesizing cefditoren pivoxil

A cefditoren pivoxil and synthetic method technology, applied in the direction of organic chemistry, etc., can solve problems such as high pressure on environmental protection, difficult recycling, complicated cefditoren pivoxil, etc., and achieve the goal of reducing production costs and environmental protection expenditures, and being easy to recycle and apply Effect

Active Publication Date: 2019-01-11
QILU ANTIBIOTICS PHARMA
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But, this method prepares the method operation of cefditoren pivoxil more complicated, and yield is on the low side, adopts mixed solvent in the synthetic process, reclaims difficulty, and environmental protection pressure is bigger

Method used

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  • Method for synthesizing cefditoren pivoxil
  • Method for synthesizing cefditoren pivoxil
  • Method for synthesizing cefditoren pivoxil

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] Embodiment 1 A kind of preparation method of cefditoren pivoxil, the preparation method comprises the following steps:

[0061] (1) Preparation of cefditoren mother nucleus: drop into 200ml of water in reaction bottle, temperature 0~10 ℃, add D-7ACA50g, add dropwise 7% sodium bicarbonate to adjust pH to dissolve clear, add sodium bromide 10g, 2,2,6,6-tetramethylpiperidine nitrogen oxide 2g, 50ml of 10% sodium hypochlorite was added dropwise, reacted for 2-3 hours, and 3N hydrochloric acid was added dropwise to adjust the pH to 3.5 to obtain about 47.08g of compound 1.

[0062] A: Put 100ml of dichloromethane into the reaction bottle, add about 23.55g of compound 1, control the temperature at 0-20°C, add hexamethyldisilazane, and react under reflux for about 5 hours to obtain the feed solution of compound 2, keep it warm 0~10℃ for later use.

[0063] B: Put 100ml of dichloromethane into the reaction bottle, add 14.4g (112mmol) of 4-methylthiazole-5-methanol, 17.7g (118m...

Embodiment 2

[0069] Embodiment 2 A kind of preparation method of cefditoren pivoxil, the preparation method comprises the following steps:

[0070] (1) Preparation of cefditoren mother nucleus: drop into 200ml of water in reaction bottle, temperature 0~10 ℃, add D-7ACA50g, add dropwise 7% sodium bicarbonate to adjust pH to dissolve clear, add sodium bromide 10g, 2,2,6,6-tetramethylpiperidine nitrogen oxide 2g, 50ml of 10% sodium hypochlorite was added dropwise, reacted for 2-3 hours, and 3N hydrochloric acid was added dropwise to adjust the pH to 3.5 to obtain about 47.08g of compound 1.

[0071] A: Put 100ml of dichloromethane into the reaction bottle, add about 23.55g of compound 1, control the temperature at 0-20°C, add hexamethyldisilazane, and react under reflux for about 5 hours to obtain the feed solution of compound 2, keep it warm 0~10℃ for later use.

[0072] B: Put 100ml of dichloromethane into the reaction bottle, add 14.4g (112mmol) of 4-methylthiazole-5-methanol, 20.1g (134m...

Embodiment 3

[0076] Embodiment 3 A kind of preparation method of cefditoren pivoxil, the preparation method comprises the following steps:

[0077] (1) Preparation of cefditoren mother nucleus: drop into 200ml of water in reaction bottle, temperature 0~10 ℃, add D-7ACA50g, add dropwise 7% sodium bicarbonate to adjust pH to dissolve clear, add sodium bromide 10g, 2,2,6,6-tetramethylpiperidine nitrogen oxide 2g, 50ml of 10% sodium hypochlorite was added dropwise, reacted for 2-3 hours, and 3N hydrochloric acid was added dropwise to adjust the pH to 3.5 to obtain about 47.08g of compound 1.

[0078] A: Put 100ml of dichloromethane into the reaction bottle, add about 23.55g of compound 1, control the temperature at 0-20°C, add hexamethyldisilazane, and react under reflux for about 5 hours to obtain the feed solution of compound 2, keep it warm 0~10℃ for later use.

[0079] B: Put 100ml of dichloromethane into the reaction bottle, add 14.4g (112mmol) of 4-methylthiazole-5-methanol, 20.1g (134m...

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Abstract

The invention relates to a method for synthesizing cefditoren pivoxil. The method comprises that D-7ACA reacts with an oxidizing reagent to produce a compound 1, the compound 1 is protected through silanization to produce a compound 2, 4-methylthiazole-5-methanol and NaI undergo an iodination reaction in the presence of a small amount of sulfuric acid for catalysis, triphenylphosphine is added into the reaction system and undergoes a reaction to produce a compound 3, the compound 3 is added into the compound 2 liquid and undergoes a reaction, the reaction product is concentrated, methanol anda small amount of concentrated hydrochloric acid are added into the concentrated product, the concentrated product is deprotected and crystallized to form cefditoren mother nucleuses, 7-ATCA and an AEactive ester undergo a reaction under alkaline conditions, the reaction product is crystallized to form a cefditoren sodium wet product, the cefditoren sodium wet product is added into iodomethyl pivalate and undergoes a reaction in the presence of a phase transfer catalyst and the product is crystallized to form a cefditoren pivoxil crude product. In preparation of the compound 1, cefditoren sodium and cefditoren pivoxil, single solvents are used and are easy to recover. The method has the advantages of simple operation, high product conversion rate, few impurities and low production cost and is suitable for industrial production of cefditoren pivoxil.

Description

technical field [0001] The invention relates to a synthesis method of cefditoren pivoxil, which belongs to the technical field of chemical drug synthesis. Background technique [0002] Cefditoren Pivoxil (Cefditoren Pivoxil), a third-generation oral cephalosporin, was pioneered by Japan's Meiji Seigakushi Co., Ltd. It went on the market in Japan in April 1994 and in China in April 2001 under the trade name of Miac. Studies have shown that cefditoren pivoxil is effective in the treatment of community-acquired respiratory tract infections caused by five major pathogenic bacteria: Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, Staphylococcus aureus, and Moraxella catarrhalis. [0003] Cefditoren Pivoxil (Cefditoren Pivoxil) chemical name is 2,2-dimethylpropionyloxymethyl (6R, 7R)-7-[(Z)-2-(2-amino-4-thiazolyl)- 2-Methoxyiminoacetamido]-3-[(Z)-2-(4-methyl-1,3-thiazol-5-yl)ethenyl]-8-oxo-5-thia- 1-Azabicyclo[4.2.0]oct-2-ene-2-carboxylate having the f...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D501/06C07D501/24
CPCC07D501/06C07D501/24
Inventor 钱山巍徐红梅孙厚斌赵振华赵爱男李凤侠侯传山
Owner QILU ANTIBIOTICS PHARMA
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