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

Preparation method of salmeterol base

A preparation step, benzyl technology, applied in the field of preparation of salmeterol, can solve the problems of excessive use of protective groups, difficult purification of intermediates, large loss of final products, etc., and achieve simple operation and post-treatment, and easy industrial production , low-cost effect

Inactive Publication Date: 2017-02-15
LUNAN PHARMA GROUP CORPORATION
View PDF9 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] In summary, the main problems in the synthetic route of salmeterol are: (1) the purification of most intermediates is difficult, resulting in a large loss in the purification process of the final product; (2) excessive use of protecting groups groups, resulting in longer reaction steps

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 salmeterol base
  • Preparation method of salmeterol base
  • Preparation method of salmeterol base

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Add 355g of compound 2, 2000ml of acetone and 212g of sodium bicarbonate into a 5L three-neck flask, stir to cool down, and dropwise add the acetone solution of compound 3 (438g dissolved in 1500ml of acetone) at 5°C, drop it in about 3 hours, and then keep it warm for reaction After 16 hours, the reaction solution was poured into 5L of ice water, extracted three times with 3000, 2000, and 1000ml of dichloromethane respectively, washed twice with 3000ml of saturated aqueous sodium chloride solution after merging, dried, and evaporated under reduced pressure to obtain approximately 580g oil 1.

[0045]Add 580g of oil 1 and 2000ml of ethanol from the previous step into a 5L reaction bottle, stir and cool down to about 10°C, add 380g of concentrated hydrochloric acid dropwise at -5°C, drop it in about 2 hours, and keep it warm for reaction. After 16 hours, add liquid base, adjust the pH to 8.2, filter with suction, wash, dry and evaporate the solvent under reduced pressure...

Embodiment 2

[0049] Add 355g of compound 2, 2000ml of THF and 212g of sodium bicarbonate into a 5L three-necked flask, stir and cool down, and add the THF solution of compound 3 (438g+1500mlTHF) dropwise at a temperature of 0°C to 20°C, drop it in about 3 hours, and then keep it warm for reaction 18 hours. After the TLC detection reaction was completed, the reaction solution was poured into 5L of ice water, extracted three times with 3000, 2000, and 1000ml of chloroform respectively, washed twice with 3000ml of saturated aqueous sodium chloride solution after merging, dried, and evaporated to remove the solvent under reduced pressure to obtain About 568 g of oil 1.

[0050] Add 568g of oil 1 and 2000ml of ethanol from the previous step into a 5L reaction bottle, stir and cool down to about 10°C, then add 360g of concentrated hydrochloric acid dropwise at 0°C, drop it in about 2 hours, keep it warm for about 17 hours, and check that the reaction is complete by TLC Afterwards, liquid causti...

Embodiment 3

[0054] Add 355g of compound 2, 2000ml of acetone and 212g of sodium bicarbonate into a 5L three-neck flask, stir to cool down, and dropwise add the acetone solution of compound 3 (438g dissolved in 1500ml of acetone) at 10°C, drop it in about 3 hours, and then keep it warm for reaction After 16 hours, the reaction solution was poured into 5L of ice water, extracted three times with 3000, 2000, and 1000ml of dichloromethane respectively, washed twice with 3000ml of saturated aqueous sodium chloride solution after merging, dried, and evaporated under reduced pressure to obtain approximately 580g oil 2.

[0055] Add 580g of oily substance 2 and 2000ml of ethanol from the previous step into a 5L reaction bottle, stir and cool down to about 10°C, add 380g of concentrated hydrochloric acid dropwise at 10°C, drop it in about 2 hours, keep it warm for reaction, and add liquid caustic soda dropwise after 16 hours , adjust the pH to 8.5, filter with suction, wash, dry and distill off th...

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 discloses a preparation method of salmeterol. The method includes the following steps: carrying out a condensation reaction on a compound 2 and a compound 3 under an alkaline condition to obtain an intermediate 4; carrying out acidic hydrolysis to obtain an intermediate 5, and reducing the intermediate 5 to obtain an intermediate 6; and removing a benzyl group from the intermediate 6 by using palladium on carbon (Pd / C) to obtain a salmeterol base. The preparation method has the advantages of mild reaction conditions, simple post-treatment, low cost, high yield high product purity, and easiness in realization of industrialization.

Description

technical field [0001] The present invention relates to the field of organic synthesis pharmacy, in particular to a preparation of salmeterol, whose chemical name is 4-(1-hydroxyl-2-(6-(4-phenylbutoxy)ethylamino)ethyl)-2- (Hydroxymethyl)phenol method. Background technique [0002] Salmeterol 7, chemical name: 4-(1-hydroxy-2-(6-(4-phenylbutoxy)ethylamino)ethyl)-2-(hydroxymethyl)phenol. [0003] [0004] Salmeterol 7 is the prodrug of salmeterol xinafoate, a new selective long-acting β2-receptor agonist whose bronchodilator effect can last for 12 hours in one dose. At the same time, salmeterol xinafoate has a strong inhibitory effect on the release of allergic reaction mediators from lung mast cells, can inhibit the early and late phase reactions induced by inhaled antigens, and reduce airway hyperresponsiveness. For asthma (including nocturnal asthma and exercise-induced asthma), asthmatic bronchitis and reversible airway obstruction. [0005] Patents such as US4992474,...

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): C07C213/08C07C217/10
CPCC07C213/08C07C221/00C07C217/10C07C225/06
Inventor 张理星白文钦王兴鹏
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