Method of synthesizing methanesulfonic acid parzhushaxing intermedinte

A technology for pazufloxacin mesylate and intermediates, which is applied in the field of synthesizing pazufloxacin mesylate intermediates, can solve the problems of high price of organic chemical reagents, difficult operation by transport workers, large losses in the extraction process, and the like. The effect of low cost, low risk factor and high product yield

Inactive Publication Date: 2006-01-25
武汉人福药业有限责任公司
View PDF0 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] 1. The second type of solvent that should be restricted is used: both dioxane and methylene chloride, the third type of solvent DMF is dimethyl sulfoxide, ethyl acetate that requires restricted use, toxic substances p-toluenesulfonic acid, Dioxane, sodium hydride, a highly dangerous substance, on the one hand brings difficulties to transportation and workers' operation; on the other hand, it brings difficulties to wastewater treatment, causes irreversible damage to the environment, and is extremely dangerous to operators;
[0010] 2. The organic chemical reagents used are expensive, which increases the cost;
[0011] 3. Ethyl acetate is used for extraction. Although it can be reused after re-distillation, the loss in the extraction process is large and the cost is high. It remains in the water phase or volatilizes, which will reduce the purity of the raw material and reduce the yield;
[0012] 4. Use concentrated hydrochloric acid and concentrated sulfuric acid to hydrolyze, the reaction time is long, and there is some pollution to the environment

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
  • Method of synthesizing methanesulfonic acid parzhushaxing intermedinte
  • Method of synthesizing methanesulfonic acid parzhushaxing intermedinte
  • Method of synthesizing methanesulfonic acid parzhushaxing intermedinte

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0026] Example 1, take 140g (S)-9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-d,e][1, 4] Ethyl benzoxazine-6-carboxylate (difluoride), 50% NaOH 500ml, use a mixture of ice and salt, the mixing ratio is 5:1, cool to below 0°C, add 20g of phase transfer catalyst PEG200 under stirring , 100g ethyl cyanoacetate, stir, carefully adjust the pH value of the solution to 6.0 with 6% dilute sulfuric acid, and slowly heat to 50°C, react for 4 hours, cool to 9°C after all the bubbles overflow, and keep the temperature at 0 Below ℃, stir slowly for 2 hours, then gradually increase the temperature to 20 ℃, keep the temperature for 4 hours, and use TLC (thin layer chromatography) to control the completion of the reaction. Freeze to -10°C, crystals precipitate out, filter with suction, and dry at 55°C to obtain 115.4g of the product, with a yield of 93.06%.

[0027] The reaction formula is as follows:

[0028]

[0029] Example 2, method and reaction formula are the same as Exa...

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 provides a process for synthesizing pazufloxacin mesylas which comprises, preparing (S)-9,10-difluoro-3-methyl-7-oxy-2,3-dihydro-7H-pyrido[1,2,3-d,e][1,4]benzene oxazine-6-carboxylic acid ethyl ester (difluoro), charging NaOH, cooling down to below 0 deg. C with ice and salt mixture, stirring and charging phase transition catalyst PEG200, ethyl cyanoacetate, stirring and adjusting pH with dilute sulphuric acid, slowly elevating the temperature to 25-60 deg. C, reacting 4-10 hours, cooling down to 2-10 deg. C, stirring 2-5 hours at below 0 deg. C, elevating the temperature to 20-25 deg. C, thermal insulating and reacting 3-8 hours, freezing, evoluting crystal, filtering by suction, finally drying to obtain the product.

Description

technical field [0001] The invention relates to a method for synthesizing an intermediate of pazufloxacin mesylate. Background technique [0002] According to literature reports, the synthesis of (S)-10-(cyanomethyl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyridine[1,2,3-d, e] [1,4]Benzoxazine-6-carboxylic acid in a two-step process. The first step, the preparation of (S)-10-(cyanoethoxycarbonylmethyl)-9-fluoro-3-methyl-7-oxo 2,3-dihydro-7H-pyrido[1,2,3 -d, e] [1,4] ethyl benzoxazine-6-carboxylate, add its weight 60% NaH64g (1.6mol) in 1250ml DMF at -5-0°C under cooling and stirring with ice salt, 300 ml of ethyl cyanoacetate with a concentration of 99% was added dropwise to the reaction solution at -5°C, and stirred for 60 minutes. (S)-9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-d,e][ 1,4] 124 g (0.4 mol) of ethyl benzoxazine-6-carboxylate. Slowly heated to 35°C and reacted for 16 hours, cooled to 25°C, and added 5000ml of ice wate...

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): C07D498/06C07D221/00C07D265/00
Inventor 邓霞飞李雪峰喻华耀吕子敏
Owner 武汉人福药业有限责任公司
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