Preparation method of ambroxol hydrochloride

A technology of ambroxol hydrochloride and ambroxol base, which is applied in the preparation of organic compounds, preparation of amino hydroxyl compounds, chemical instruments and methods, etc., can solve problems such as environmental pollution, and achieve reduction of environmental pollution, easy operation, and short reaction time shortening effect

Inactive Publication Date: 2013-04-03
石药集团中诺药业(石家庄)有限公司
View PDF5 Cites 27 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, multiple solvents such as dichloromethane and tetrachloroethylene are used in

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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Add 100ml of methanol, 2-amino-3,5-dibromobenzaldehyde (10.0g, 35.9mmol), trans-4-aminocyclohexanol (5.0g, 43.4mmol) into the reaction kettle, and heat to Reflux (60°C-65°C), keep warm for 6 hours, TLC monitors that the reaction is complete, then cool down to 30°C-40°C, add sodium borohydride (2.1g, 55.5mmol), add, keep warm for 6h, TLC monitors the reaction is complete After the heat preservation is completed, cool the reaction solution to 10°C-20°C, adjust the pH value to 1 with hydrochloric acid solution under stirring, lower the temperature to 5°C-10°C, keep the temperature for 6 hours, filter, rinse, and dry to obtain the crude product of ambroxol hydrochloride 12.1g, yield 81.4%, purity 99.30%.

[0036] Take 10g of ambroxol hydrochloride crude product, slowly add 70ml of 30% methanol aqueous solution under stirring, heat to reflux until completely dissolved, decolorize activated carbon, lower the temperature, keep warm and crystallize at 0℃~5℃ for 8h, filter, rins...

Embodiment 2

[0038] Add 100ml of methanol, 2-amino-3,5-dibromobenzaldehyde (10.0g, 35.9mmol), trans-4-aminocyclohexanol (5.0g, 43.4mmol) into the reaction kettle, and heat to Reflux (60°C-65°C), keep warm for 3 hours, TLC monitors that the reaction is complete, then cool down to 30°C-35°C, add sodium borohydride (1.63g, 43.1mmol), after addition, keep warm for 6h, TLC monitors that the reaction is complete After the heat preservation is completed, cool the reaction solution to 10°C-20°C, adjust the pH value to 2 with hydrochloric acid solution under stirring, lower the temperature to 0°C-5°C, keep the temperature for 4 hours, filter, rinse, and dry to obtain the crude product of ambroxol hydrochloride 13.0g, yield 87.5%, purity 99.48%.

[0039] Take 10g of ambroxol hydrochloride crude product, slowly add 70ml of 50% methanol aqueous solution under stirring, heat to reflux, until completely dissolved, decolorize activated carbon, cool down, keep warm and crystallize at 0℃~5℃ for 8h, filter,...

Embodiment 3

[0041]Add 100ml of methanol, 2-amino-3,5-dibromobenzaldehyde (10.0g, 35.9mmol), trans-4-aminocyclohexanol (4.53g, 39.3mmol) into the reaction kettle, and heat to Reflux (60°C-65°C), keep warm for 8 hours, TLC monitors that the reaction is complete, then cool down to 20°C-30°C, add lithium aluminum hydride (1.63g, 43.0mmol), after addition, keep warm for 6h, TLC monitors that the reaction is complete After the heat preservation is completed, cool the reaction solution to 10°C-20°C, adjust the pH value to 2 with hydrochloric acid solution under stirring, cool down to 10°C-15°C, keep the temperature for 5 hours, filter, rinse, and dry to obtain the crude product of ambroxol hydrochloride 12.3g, yield 82.8%, purity 99.27%.

[0042] Take 10g of ambroxol hydrochloride crude product, slowly add 200ml of mixed solution of methanol and acetone (volume ratio 1:3) under stirring, heat to reflux, until completely dissolved, decolorize activated carbon, cool down, keep warm and crystallize...

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 ambroxol hydrochloride. According to the preparation method, a 'one-pot reaction' is adopted in the reaction, so that the separation of an intermediate is avoided, the operation is simple, the production period is short, the production cost is reduced, and the method is suitable for industrial production and application; the operation in refining the ambroxol hydrochloride is easy to carry out; and the ambroxol hydrochloride with purity more than 99.9% can be simply obtained by one-time recrystallization, so that the demand on preparation production can be met.

Description

technical field [0001] The invention belongs to the technical field of medicines, and relates to a preparation method of ambroxol hydrochloride, in particular to a process for preparing ambroxol hydrochloride by adopting a one-pot method. Background technique [0002] Ambroxol hydrochloride, the chemical name is: trans-4-[(2-amino-3,5-dibromobenzyl) amino]-cyclohexanol hydrochloride, the chemical structure is: [0003] . [0004] Ambroxol hydrochloride is a mucolytic agent developed by Boehringer Ingelheim, Germany. It is used for the expectorant treatment of various acute and chronic respiratory diseases accompanied by abnormal sputum secretion and poor expectoration function. low merit. Ambroxol hydrochloride can act on secretory cells, regulate the secretion of serous and mucus, increase the secretion of serous, dissolve and dilute mucus, strengthen the swing of cilia, increase the removal ability of mucus transport system, and make sputum easy to discharge. [0005]...

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): C07C215/44C07C213/08
Inventor 张延峰杨红伟牛劲
Owner 石药集团中诺药业(石家庄)有限公司
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

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