Efficient production method of bromhexine hydrochloride

A technology of bromhexine hydrochloride and its production method, which is applied in the production field of bromhexine hydrochloride, can solve the problems of high production cost, low yield, non-environmental protection, etc., achieve the improvement of purity and yield, reduce reaction temperature, and reduce consumption Effect

Pending Publication Date: 2021-01-26
江西亿友药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] However, this process has many defects such as high production cost, environmental protection and low yield.

Method used

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  • Efficient production method of bromhexine hydrochloride
  • Efficient production method of bromhexine hydrochloride
  • Efficient production method of bromhexine hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0081] Embodiment 1 (new process)

[0082] 1, Preparation of 3,5-dibromo-2-aminobenzyl alcohol

[0083]

[0084] Put 240kg of absolute ethanol and 100kg of 3,5-dibromo-2-aminobenzaldehyde into the cleaned and dried 1000L glass-lined reactor. After stirring evenly, slowly add 9 kg of potassium borohydride in 6 times to control the reaction temperature The reaction temperature was not higher than 50° C., stirred for 3 hours, and the reaction of the raw materials was checked by TLC. After the reaction is complete, the reaction solution is placed in a 2000L reactor and cooled to 0-10°C for crystallization. Put the clean centrifuge filter bag well, put the material into the centrifuge for spin filtration, wash the material with water until neutral (check with pH test paper), and spin dry. Put the dried intermediate into a clean stainless steel tray, spread it evenly, with a thickness of 1-2 cm, place it on the drying frame, push it into the hot air circulation oven, turn off t...

Embodiment 2

[0099] Embodiment 2 (new technology)

[0100] 1. Synthesis of 3,5-dibromo-2-aminobenzyl alcohol

[0101]

[0102] In the cleaned and dried 1000L glass-lined reactor, drop into 240kg of absolute ethanol, 3,5-dibromo-2-aminobenzaldehyde 100kg, after stirring evenly, slowly add potassium borohydride 12kg in 6 times, control the reaction temperature as 20° C., stirred for 3 hours, and TLC checked that the raw materials were completely reacted. After the reaction is complete, the reaction solution is placed in a 2000L reactor and cooled to 0-10°C for crystallization. Put the clean centrifuge filter bag well, put the material into the centrifuge for spin filtration, wash the material with water until neutral (check with pH test paper), and spin dry. Put the dried intermediate into a clean stainless steel tray, spread it evenly, with a thickness of 1-2cm, place it on the drying frame, push it into the hot air circulation oven, turn off the oven, turn on the power to heat up to 8...

Embodiment 3

[0110] Embodiment 3 (new process)

[0111] 1. Synthesis of 3,5-dibromo-2-aminobenzyl alcohol

[0112]

[0113] In the cleaned and dried 1000L glass-lined reactor, drop into 240kg of dehydrated alcohol, 3,5-dibromo-2-aminobenzaldehyde 100kg, after stirring evenly, slowly add potassium borohydride 6kg in 6 times, control the reaction temperature as 60° C., stirred for 3 hours, and TLC checked that the reaction of the raw materials was complete. After the reaction is complete, the reaction solution is placed in a 2000L reactor and cooled to 0-10°C for crystallization. Put the clean centrifuge filter bag well, put the material into the centrifuge for spin filtration, wash the material with water until neutral (check with pH test paper), and spin dry. Put the dried intermediate into a clean stainless steel tray, spread it evenly, with a thickness of 1-2cm, place it on the drying frame, push it into the hot air circulation oven, turn off the oven, turn on the power to heat up t...

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PUM

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Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to an efficient production method of bromhexine hydrochloride. The production method of bromhexine hydrochloride comprises the following steps: (1) reducing 3,5-dibromo-2-aminobenzaldehyde by a reducing agent to obtain an intermediate 3,5-dibromo-2-aminobenzyl alcohol; (2) reacting the intermediate 3,5-dibromo-2-aminobenzyl alcohol with N-methylcyclohexylamine, and then carrying out salt forming reaction to obtain a bromhexine hydrochloride crude product; and (3) purifying the bromhexine hydrochloride crude product to obtain the bromhexine hydrochloride.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a high-efficiency production method of bromhexine hydrochloride. Background technique [0002] Bromhexine hydrochloride is a mucolytic agent that can directly act on the bronchial glands to promote the release of lysosomes in mucus-secreting cells, which can differentiate and lyse mucopolysaccharide fibers in sputum, dilute the sputum, and make it easier to cough up. Clinically, it is mainly used for acute and chronic bronchitis, asthma, bronchiectasis, and emphysema, especially for those who have difficulty coughing up white sticky phlegm and critical emergencies caused by extensive obstruction of small bronchi by sputum. Bromhexine hydrochloride preparations have various dosage forms such as oral tablets, solutions, aerosols, injections, freeze-dried powder injections, and large infusions. [0003] Bromhexine hydrochloride was developed by Boehringer Ingelheim ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C211/52C07C209/68C07C209/00C07C209/84C07C215/68C07C213/00
CPCC07C209/68C07C209/00C07C209/84C07C213/00C07C2601/14C07C211/52C07C215/68
Inventor 徐卫国张文轩杨庆云吴松张嵩张对良薛丹贾雨晴
Owner 江西亿友药业有限公司
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