Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Linezolid preparation method

A technology of linezolid and triethylamine, applied in the field of preparation of linezolid, can solve the problems of low total yield, high cost, difficulty in industrial production of linezolid, etc., achieve mild and easy-to-control reaction conditions, simplify operation, avoid Effect of column separation process

Active Publication Date: 2013-12-04
LUNAN PHARMA GROUP CORPORATION
View PDF8 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0029] To sum up, in the synthetic route mentioned above, there is a widespread use of explosive sodium azide, or the use of n-butyllithium in an anhydrous and oxygen-free ultra-low temperature environment, or high-pressure catalytic hydrogenation, or the use of violent Toxic phosgene, low total yield, and high cost have brought certain difficulties to the industrial production of linezolid

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
  • Linezolid preparation method
  • Linezolid preparation method
  • Linezolid preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Example 1 Preparation of 3-fluoro-4-morpholine nitrobenzene

[0055] In a 3L three-necked flask, install a mechanical stirrer and a thermometer respectively, add 150g (1.72mol) of morpholine, 175g (1.73mol) of triethylamine and 800mL of ethyl acetate, stir well at room temperature, and slowly add 3,4-difluoro 250g (1.57mol) of nitrobenzene was added dropwise within 40min, and stirred at room temperature for 24h, a large amount of yellow solid was formed. TLC showed that the reaction was complete. The reaction mixture was poured into 2.8L of ethyl acetate, fully stirred to dissolve, the solution was washed with water and saturated brine respectively, separated, dried, filtered, and the filtrate was concentrated and crystallized to obtain 351.3 g of a golden yellow solid. The yield is 99.0%.

Embodiment 2

[0056] Example 2 Preparation of 3-fluoro-4-morpholine aniline

[0057] In a 3L three-necked flask, add a mechanical stirrer and a thermometer respectively, add 100g (0.44mol) of 3-fluoro-4-morpholine nitrobenzene, 1L of acetone, 3.0g of 10%Pd / C and 137.5g (2.18mol) of ammonium formate ), fully stirred, heated up to 50°C, stirred and reacted for 8 hours, TLC showed that the reaction had been completed, then added 500 mL of acetone, stirred evenly, aged for 2 hours, filtered, and the filtrate was concentrated to dryness to obtain 96 g of off-white solid, the product was not purified. used directly in the next reaction.

Embodiment 3

[0058] Example 3 Preparation of N-benzyloxycarbonyl-3-fluoro-4-morpholinoaniline

[0059] In a 3L three-necked flask, add 96g of unpurified 3-fluoro-4-morpholine aniline, 1.8L of acetone, 800mL of water and 73.9g (0.88mol) of sodium bicarbonate, stir well, and cool down to 0~5°C in an ice-water bath , and then slowly dropwise added 90.0 g (0.53 mol) of benzyl chloroformate, after the dropwise addition was completed, it was slowly raised to room temperature, and the reaction was stirred overnight. The reaction mixture was poured into ice water to precipitate a solid, which was left to stand for 2 h, filtered, washed with water and ethanol, and dried to obtain 132 g of an off-white solid with a yield of 91.0%.

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 linezolid (1) preparation method. The method comprises the following steps: reacting a raw material 3,4-difluoronitrobenzene with morpholine, reducing, reacting with benzyl chloroformate to obtain N-benzyloxycarbonyl-3-fluoro-4-morpholinylaniline, carrying out a ring closure reaction of N-benzyloxycarbonyl-3-fluoro-4-morpholinylaniline and (S)-N-(2,3-epoxypropyl)phthalimide, ammonolyzing, and acetylating to obtain linezolid (1).

Description

technical field [0001] The invention relates to a new method for preparing oxazolidinone antibacterial agents. In particular the invention relates to a novel process for the preparation of linezolid. Background technique [0002] Linezolid, the English name is Linezolid, the chemical name is (S)-N-{[3-(3-fluoro-4-(4-morpholinyl)phenyl)-2-oxo-5-oxazolinyl ]methyl}acetamide. The molecular formula of linezolid is C 16 h 20 FN 3 o 4 , with a molecular weight of 337.35, it is a white solid with a melting point of 181.0-183.0°C, and its structural formula is as follows: [0003] [0004] Linezolid is the first synthetic oxazolidinone antibiotic, which was researched and developed by Pharmacia & Upjhon Company of the United States. It was approved for marketing by the FDA on April 18, 2000, and its trade name is ZYVOX. The drug can treat nosocomial pneumonia, skin and soft tissue infection, community infectious pneumonia and other diseases, and its efficacy has been confi...

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): C07D263/20
Inventor 王红波赵荐飞陈见见
Owner LUNAN PHARMA GROUP CORPORATION
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com