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A kind of betahistine synthesis method

A technology of betahistine and synthetic method, which is applied in the field of betahistine synthesis, can solve the problems that the product yield cannot reach this level, strict production conditions, poor control, etc., and achieve high product yield and low reaction temperature Low, good safety performance

Active Publication Date: 2022-07-12
HEBI SAIKE CHEM ENG CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The process has less pollution, higher yield, and the produced by-products can be recycled, but the production conditions are strict, and there are strict restrictions on the amount of feed, the amount of catalyst, and the entry of water, and at the end of the reaction, excess acetylene polymerizes to form benzene, which is a strong Exothermic reaction, instantaneous high temperature and high pressure, poor control may easily lead to safety accidents
Therefore, under various reasons, although the yield in the laboratory can reach more than 90%, the product yield in the actual process production is far from reaching this level
In the prior art, there is no report of using this process route to synthesize betahistine

Method used

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  • A kind of betahistine synthesis method
  • A kind of betahistine synthesis method
  • A kind of betahistine synthesis method

Examples

Experimental program
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Effect test

Embodiment 1

[0048] The method for synthesizing betahistine provided in this embodiment includes the following steps: put 100kg of 3-methylaminopropionitrile, 100kg of xylene, and 0.3kg of cyclopentadienyl cobalt as a catalyst in a 1000L high-pressure reaction kettle, and at a negative pressure of 0.09MPa Next, replace it with high-purity nitrogen three times, pass purified and dry acetylene gas to 0.1MPa, heat it to 70°C, and then continue to feed acetylene gas, keep the temperature at 85°C, and control the pressure at about 0.6MPa. When the acetylene is produced, the pressure in the reactor rises sharply. At this time, the reaction ends, and the injection of acetylene gas is stopped. The pressure drops to 0.08MPa, and the temperature drops to 40°C. Except for the solvent, the crude product of betahistine with a content of 82% and 2 % of the by-product benzene and about 15% of unreacted raw materials and other impurities, the yield is greater than 80%.

Embodiment 2

[0050] The method for synthesizing betahistine provided by this embodiment includes the following steps: put 100kg of 3-methylaminopropionitrile, 600kg of benzene, and 5kg of cyclopentadienyl cobaltocene as a catalyst in a 1000L autoclave, and under a negative pressure of 0.09MPa , replaced three times with high-purity nitrogen, introduced purified and dried acetylene gas to 0.1MPa, heated to 65°C, and then continued to feed acetylene gas, controlled the temperature at 95°C, and controlled the pressure at about 0.8MPa. During acetylene, the pressure in the reaction kettle rose sharply. At this time, the reaction was over, and the injection of acetylene gas was stopped. The pressure dropped to 0.08MPa, and the temperature dropped to 40°C. Except for the solvent, the content of betahistine was 88% crude and 2% betahistine was obtained. The by-product benzene and about 10% unreacted raw materials and other impurities have a yield greater than 85%.

Embodiment 3

[0052] The betahistine synthesis method that the present embodiment provides, comprises the steps: drop into 100kg of 3-methylaminopropionitrile, toluene 250kg, catalyst a 2kg (catalyst a is 1:0.55 bisocene by mol ratio) in the autoclave of 1000L Cobalt and azobisisobutyronitrile are reacted in 5 times the molar amount of tetrahydrofuran), at a negative pressure below 0.09MPa, replace it with high-purity nitrogen three times, pass purified and dry acetylene gas to 0.1MPa, and heat to 65 ℃ , and then continue to feed acetylene gas, control the temperature at 90°C, and control the pressure at about 0.9MPa. When feeding 65kg of acetylene, the pressure in the reactor rises sharply. At this time, the reaction ends, stop injecting acetylene gas, and the pressure drops to 0.08MPa , the temperature was lowered to 40°C, and the content of crude betahistine was 96%, 2% of by-product benzene and 2% of unreacted raw materials and other impurities were obtained except for the solvent, and t...

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Abstract

The invention discloses a method for synthesizing betahistine, which comprises the following steps: taking 3-methylaminopropionitrile, a solvent, a monovalent cobaltocene catalyst, and acetylene in an anhydrous and oxygen-free environment at 85-95° C. The betahistine is synthesized through a cyclization reaction under a certain reaction pressure. The method for synthesizing betahistine provided by the invention has simple steps, adopts 3-methylaminopropionitrile and acetylene to synthesize in one step, has low reaction temperature, good safety performance, high utilization rate of raw materials, and can reduce the need for products in multi-step reactions. loss, the product yield is high. Second, the reaction is an anhydrous reaction, which can avoid the generation of a large amount of waste water and alkali-containing hazardous waste generated from 2-vinylpyridine as a raw material.

Description

technical field [0001] The invention belongs to the technical field of chemical production, and particularly relates to a method for synthesizing betahistine. Background technique [0002] Betahistine, also known as 2-(2-methylaminoethyl)pyridine, is easily soluble in water, slightly soluble in absolute ethanol, and insoluble in propanol. It is odorless, slightly bitter in taste and easy to deliquesce. It is an important drug for Meniere's syndrome, vascular headache and cerebral arteriosclerosis. [0003] At present, a main synthetic method is as follows: using 2-methylpyridine as raw material, adding formaldehyde to obtain 2-hydroxyethylpyridine, then adding sodium hydroxide for dehydration to obtain 2-vinylpyridine, and then adding methylamine hydrochloride in toluene Addition in a solvent gives betahistine hydrochloride. The synthesis method has many steps, the product is seriously lost in the preparation process, the 2-vinylpyridine wastewater produced by the method i...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D213/38B01J31/22
CPCC07D213/38B01J31/2295Y02P20/584
Inventor 郜家军蔡东旭
Owner HEBI SAIKE CHEM ENG CO LTD
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