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

Preparation method of salbutamol intermediate V hydrochloride

A technology of albuterol and intermediates, applied in the field of preparation of albuterol intermediate V hydrochloride

Inactive Publication Date: 2018-10-09
CHONGQING CONQUER PHARML
View PDF4 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The technical problem to be solved by the present invention is to provide a preparation method of albuterol intermediate V hydrochloride, the preparation method provided by the present invention solves the problem of avoiding the introduction of class I solvent benzene, and is also conducive to further improving product quality

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 salbutamol intermediate V hydrochloride
  • Preparation method of salbutamol intermediate V hydrochloride
  • Preparation method of salbutamol intermediate V hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0021] A preparation method of salbutamol intermediate V hydrochloride is as follows: intermediate IV and N-benzyl tert-butylamine are refluxed in the reaction solvent ethyl acetate, filtered, acidified, and the product is extracted into the water layer, hydrolyzed under reflux, Alkalinization, extraction with ethyl acetate, concentration to obtain the free base of intermediate V, the concentrated free base was dissolved in an organic solvent, and aqueous hydrochloric acid was added dropwise to obtain the hydrochloride of intermediate V. The process route is as follows:

[0022]

Embodiment 1

[0023] Embodiment one: the preparation of intermediate IV

[0024] Referring to the patent US3642896, add intermediate III to chloroform, stir and cool to 20°C, and then dissolve bromine in the solution. After completion, water was added to the mixture, and the chloroform layer was separated, washed with water and dried over sodium sulfate. Chloroform was evaporated in vacuo to afford Intermediate IV.

Embodiment 2

[0025] Embodiment two: the preparation of intermediate V hydrochloride

[0026] Dissolve 20g of intermediate IV in 300ml of ethyl acetate, add 25.9g of N-benzyl tert-butylamine, heat to reflux for 15 hours, cool down to 20-25°C, filter, add 32g of hydrochloric acid aqueous solution diluted with 300ml of water to the filtrate, stir and extract, separate solution to obtain the water layer, heat the water layer to reflux for 4 hours, lower the temperature to 20-25°C, add 300ml of ethyl acetate, adjust the pH to 9 with sodium carbonate, separate the layers to obtain the ethyl acetate layer, and concentrate the ethyl acetate under reduced pressure at 50°C After the solution was added, 150ml of tetrahydrofuran was added, 2.4g of hydrochloric acid was added dropwise, kept at 20-30°C and stirred for 1h, cooled to 0-5°C and stirred for 1h, filtered, and dried under reduced pressure at 50°C to obtain 14.62g of intermediate V hydrochloride with a purity of 97.5 %.

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

Salbutamol is a beta receptor stimulant. In the conventional preparation technology of salbutamol, reference listed drug technology is taken as the main research content; in the reference listed drugtechnology, p-Hydroxyacetophenone is taken as an initial material, chloromethylation, esterification, bromination, amination, hydrolysis, and reduction are adopted to prepare salbutamol. According tothe reparation method of salbutamol intermediate V hydrochloride, intermediate IV and N-Benzyl-tert-butylamine are subjected to backflow reaction in reaction solvent ethyl acetate, and filtering and acidifying are carried out so as to realize product extraction into a water layer, hydrolysis and alkalization are carried out at backflow states, extractant ethyl acetate is adopted for extraction, and concentration is carried out so as to obtain a free alkali compound of the intermediate V; and the free alkali is dissolved in an organic solvent, and hydrochloric acid is added dropwise so as to obtain the salbutamol intermediate V hydrochloride.

Description

technical field [0001] The invention relates to the field of medicine and chemical industry, in particular to a preparation method of albuterol intermediate V hydrochloride. Background technique [0002] Salbutamol is a beta-receptor agonist mainly used in the treatment of bronchospasm caused by wheezing bronchitis, bronchial asthma, and emphysema. Due to the frequent occurrence of global respiratory diseases, the consumption of salbutamol also remains high. At present, the preparation process of salbutamol is mainly based on the original research process. The original research process uses p-hydroxyacetophenone as the starting material, and prepares salbutamol through chloromethylation, esterification, bromination, amination, hydrolysis and reduction. The route is as follows: [0003] [0004] In the above synthetic route, toluene is used as the reaction solvent in the preparation of intermediate IV from intermediate IV, and benzene, a class I solvent, is introduced, r...

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): C07C225/06C07C221/00C07C67/287C07C67/11C07C69/16C07C45/68C07C49/825
CPCC07C45/68C07C67/11C07C67/287C07C221/00C07C49/825C07C69/16C07C225/06
Inventor 陈用芳朱元波徐刚胡延贵余灏杨绪凤蒋其斌李斌
Owner CHONGQING CONQUER PHARML
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