Preparation method of Cefditoren Pivoxil

A technology of cefditoren pivoxil and its compounds, which is applied in the field of preparation of cefditoren pivoxil, can solve problems such as yield reduction, messy reaction, difficult purification process, etc., and achieve increased reactivity, mild reaction conditions, and product purity high effect

Active Publication Date: 2018-05-29
SHANDONG YUXIN PHARMA CO LTD
View PDF12 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But in this method, become sodium salt reaction, need to react under strong alkali, the amide bond etc. in the product can be destroyed to a certain extent, then react with iodomethyl pivalate again, cause reaction messy, many by-products, Yield decreased, and due to by-products (such as Δ 3 isomer, E isomer, etc.) are similar to the product in nature and structure, the purification process is particularly difficult, and the sodium salt of cefditoren acid is not suitable for storage and has poor stability
In addition, there are few studies on the starting material 7-ATCA at present, and most of the existing technologi

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation method of Cefditoren Pivoxil
  • Preparation method of Cefditoren Pivoxil
  • Preparation method of Cefditoren Pivoxil

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Step 1) Under nitrogen protection, 10.89g 3-acetoxymethyl-5-thio-7-amino-8-oxo-1-azabicyclooct-2-ene-2carboxylic acid, 100mL acetonitrile, 46mmol N , put O-bistrimethylsilylacetamide (BSA) in the reaction bottle, stir the reaction at room temperature for 4h, add dropwise N,N-diethylaniline 4~6mL, trimethyl iodosilane (TMSI) 44mmol, in 10~ React at 15°C for 1 hour, add 11.02 g of triphenylphosphine, continue the reaction for 1 hour, add 7.34 g of sodium hexamethyldisilazide, stir at room temperature for 45 minutes, separate the organic layer and wash with water, then wash with 20% w / w NaCl aqueous solution, Anhydrous MgSO 4 After drying, 22.01 g of compound 4 was obtained, with a yield of 89%.

[0038] Step 2)

[0039] [C 4 MIm]PF 6 Preparation of ionic liquid: 6.896g KPF will be dissolved 6 50mL of acetone solution was placed in a 250mL three-necked flask, and then 10mL containing 5.47g [C 4 MIm]Br in acetone solution, a white precipitate appeared immediately, aft...

Embodiment 2

[0044] Step 1) Under nitrogen protection, 10.89g of 3-acetoxymethyl-5-thio-7-amino-8-oxo-1-azabicyclooct-2-ene-2carboxylic acid, 100mL of acetonitrile, 40mmol N , put O-bistrimethylsilylacetamide (BSA) in the reaction bottle, stir the reaction at room temperature for 4h, add dropwise N,N-diethylaniline 4~6mL, trimethyl iodosilane (TMSI) 40mmol, in 10~ React at 15°C for 1 hour, add 10.49 g of triphenylphosphine, continue the reaction for 1 hour, add 7.34 g of sodium hexamethyldisilazide, stir at room temperature for 45 minutes, separate the organic layer and wash with water, then wash with 20% w / w NaCl aqueous solution, Anhydrous MgSO 4 After drying, 19.79 g of compound 4 was obtained, with a yield of 80%.

[0045] Step 2)

[0046] [C 4 MIm]PF 6 Preparation of ionic liquid: 6.896g KPF will be dissolved 6 50mL of acetone solution was placed in a 250mL three-necked flask, and then 10mL containing 5.47g [C 4 MIm]Br in acetone solution, a white precipitate appeared immediatel...

Embodiment 3

[0051] Step 1) Under nitrogen protection, 10.89g of 3-acetoxymethyl-5-thio-7-amino-8-oxo-1-azabicyclooct-2-ene-2carboxylic acid, 100mL of acetonitrile, 52mmol N , put O-bistrimethylsilylacetamide (BSA) in the reaction bottle, stir the reaction at room temperature for 4h, add dropwise N,N-diethylaniline 4~6mL, trimethyl iodosilane (TMSI) 40mmol, in 10~ React at 15°C for 1 hour, add 11.54 g of triphenylphosphine, continue the reaction for 1 hour, add 7.34 g of sodium hexamethyldisilazide, stir at room temperature for 45 minutes, separate the organic layer and wash with water, then wash with 20% w / w NaCl aqueous solution, Anhydrous MgSO 4 After drying, 20.78 g of compound 4 was obtained, with a yield of 84%.

[0052] Step 2)

[0053] [C 4 MIm]PF 6 Preparation of ionic liquid: 6.896g KPF will be dissolved 6 50mL of acetone solution was placed in a 250mL three-necked flask, and then 10mL containing 5.47g [C 4 MIm]Br in acetone solution, a white precipitate appeared immediatel...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention relates to a preparation method of Cefditoren Pivoxil. The preparation method comprises steps as follows: 7-ACA (3-acetyloxymethyl-5-thio-7-amino-8-oxy-1-nitrogen heterobicyclic octyl-2-ene-2 carboxylic acid) is taken as a starting raw material and is subjected to iodination and Wittig reaction after silanization protection, and a Cefditoren parent nucleus 7-ATCA (7-amino-3-[(Z)-2-(4-methyl-5-thiazole) vinyl]-3-cephem-4-carboxylic acid) is generated; after amino protection of aminothiazole ethyl gallate, a compound 2 is produced from 7-ATCA under catalysis of AlMe3; the compound2 is subjected to an esterification reaction with iodomethyl pivalate under actions of a phase transfer catalyst and an acid adsorbent, the amino protection is removed, and a target product CefditorenPivoxil is obtained. According to the preparation method, reaction conditions are mild, product purity and yield are high, the process is stable, amplification is easy, and the method is applicable to industrial production.

Description

technical field [0001] The invention relates to the technical field of medicines, in particular to a preparation method of cefditoren pivoxil. Background technique [0002] Cefditoren Pivoxil (Cefditoren Pivoxil), chemical name: 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, a third-generation cephalosporin antibacterial drug, was developed by the Japanese Meiji Seika Company and was launched in Japan in 1994 under the trade name Meiact. This product is mainly used to treat infections caused by Gram-positive bacteria and Gram-negative bacteria, including infections caused by Streptococcus pneumoniae, Klebsiella pneumoniae, Staphylococcus aureus, Proteus, etc. the therapeutic effect. Its structural formula is as follows: [0003] [0004] Several preparation methods that have been reported about the synthesis of cefdito...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C07D501/24C07D501/04
CPCC07D501/04C07D501/24
Inventor 刘振腾陈雨张金宝王平
Owner SHANDONG YUXIN PHARMA CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap