A kind of preparation method of zolmitriptan intermediate

A technology for intermediates and crystals, which is applied in the field of preparation of zolmitriptan intermediates, can solve the problems of fire, difficult centrifugation of iron sludge, unfriendly environment, etc., and achieves the effects of mild reaction conditions, simple post-processing and environmental friendliness

Active Publication Date: 2021-04-06
济南立德医药技术有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] (1) Iron sludge will be produced during the reaction process, which is difficult to centrifuge and produces a large amount of waste solids, which is not friendly to the environment;
[0005] (2) In order to maintain the high activity of the catalyst, a considerable amount of hydrazine hydrate must be used to compensate for the loss caused by the self-lysis of hydrazine hydrate, and the activated carbon stained with hydrazine hydrate is also in danger of fire if it is placed in the air for a long time, and the safety hazard is relatively large.

Method used

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  • A kind of preparation method of zolmitriptan intermediate

Examples

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Effect test

Embodiment 1

[0019] A preparation method of zolmitriptan intermediate, using (S)-4-(4-nitrobenzyl)-2-oxazolidinone as raw material, adopting palladium charcoal and ammonium formate to react with it, prepared Zolmitriptan intermediate (S)-4-(4-aminobenzyl)-2-oxazolidinone.

[0020] The specific steps are: add (S)-4-(4-nitrobenzyl)-2-oxazolidinone into DMF, add palladium carbon under stirring condition, control the reaction temperature at 50°C, and add ammonium formate in batches , the addition is complete, keep warm until the reaction is complete, filter, add water dropwise to the filtrate, keep the temperature at 10°C and stir and crystallize for 2 hours, filter to obtain light yellow crystals, namely (S)-4-(4-aminobenzyl)- 2-oxazolidinone, melting point: 93-96 degrees, yield 95.3%, purity 98.2%.

[0021] In terms of molar ratio, (S)-4-(4-nitrobenzyl)-2-oxazolidinone:ammonium formate=1:5.

[0022] The amount of palladium carbon added is 4% of the mass of (S)-4-(4-nitrobenzyl)-2-oxazolidi...

Embodiment 2

[0027] A preparation method of zolmitriptan intermediate, using (S)-4-(4-nitrobenzyl)-2-oxazolidinone as raw material, adopting palladium charcoal and ammonium formate to react with it, prepared Zolmitriptan intermediate (S)-4-(4-aminobenzyl)-2-oxazolidinone.

[0028] The specific steps are: add (S)-4-(4-nitrobenzyl)-2-oxazolidinone into dioxane, add palladium carbon under stirring condition, control the reaction temperature at 60°C, and batch Add ammonium formate, after the addition is complete, keep warm until the reaction is complete, filter, add water dropwise to the filtrate, keep the temperature at 0°C, stir and crystallize for 3 hours, filter to obtain light yellow crystals, namely (S)-4-(4-aminobenzyl base)-2-oxazolidinone, melting point: 93-96 degrees, yield 95.8%, purity 98.7%.

[0029] In terms of molar ratio, (S)-4-(4-nitrobenzyl)-2-oxazolidinone:ammonium formate=1:5-6.

[0030] The amount of palladium carbon added is 6% of the mass of (S)-4-(4-nitrobenzyl)-2-oxa...

Embodiment 3

[0035] A preparation method of zolmitriptan intermediate, using (S)-4-(4-nitrobenzyl)-2-oxazolidinone as raw material, adopting palladium charcoal and ammonium formate to react with it, prepared Zolmitriptan intermediate (S)-4-(4-aminobenzyl)-2-oxazolidinone.

[0036] The specific steps are: add (S)-4-(4-nitrobenzyl)-2-oxazolidinone into DMF, add palladium carbon under stirring condition, control the reaction temperature at 55°C, and add ammonium formate in batches , the addition is complete, keep warm until the reaction is complete, filter, add water dropwise to the filtrate, keep the temperature at 5°C and stir and crystallize for 2.5 hours, filter to obtain light yellow crystals, namely (S)-4-(4-aminobenzyl)- 2-Oxazolidinone, melting point: 93-96 degrees, yield 96.2%, purity 99.1%.

[0037] In terms of molar ratio, (S)-4-(4-nitrobenzyl)-2-oxazolidinone:ammonium formate=1:5-6.

[0038] The amount of palladium carbon added is 5% of the mass of (S)-4-(4-nitrobenzyl)-2-oxazol...

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Abstract

The invention belongs to the technical field of organic synthesis, and in particular relates to a preparation method of a zolmitriptan intermediate. The present invention takes (S)-4-(4-nitrobenzyl)-2-oxazolidinone as raw material, adopts palladium carbon and ammonium formate to react with it, and prepares zolmitriptan intermediate (S)- 4‑(4‑aminobenzyl)‑2‑oxazolidinone. The invention adopts ammonium formate and palladium charcoal for reduction, has low reaction temperature, simple post-treatment, is environmentally friendly, and the catalyst can be recycled and used mechanically. Adopting the present invention, the yield is above 95%, and the purity is above 98%.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a preparation method of a zolmitriptan intermediate. Background technique [0002] Zolmitriptan, chemical name (S)-4-[3-[2-(dimethylamino)ethyl]-1H-indole-5-methyl]-2-oxazolidinone, is An anti-migraine drug developed by Glaxo-Wellcome in Germany, it is a highly selective serotonin (5-TH1B and 5-TH1D) receptor agonist, which stimulates intracranial blood vessels (including arteriovenous anastomosis) ) and 5-HTIB / ID receptors on the sympathetic nerves of the trigeminal nervous system, constrict blood vessels and inhibit the release of neuropeptides to relieve migraine attacks. At present, it has been listed in the United Kingdom, the United States and other countries, and the market prospect is good. [0003] (S)-4-(4-aminobenzyl)-2-oxazolidinone is an important intermediate in the synthesis of zolmitriptan. At present, (S)-4-(4-aminobenzyl)-2-oxazolidinone...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D263/20
CPCC07B2200/07C07D263/20Y02P20/584
Inventor 陈祝功
Owner 济南立德医药技术有限公司
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