Betahistine synthesis method

A synthetic method, the technology of betahistine, 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: 2020-11-03
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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Embodiment 1

[0048] The synthesis method of betahistine provided in this embodiment comprises the following steps: 100kg of 3-methylaminopropionitrile, 100kg of xylene, 0.3kg of catalyst cyclopentadienyl cobalt are put into a 1000L autoclave, Next, replace it with high-purity nitrogen three times, pass in purified and dry acetylene gas to 0.1MPa, heat up to 70°C, then continue to pass in acetylene gas, keep the temperature at 85°C, and control the pressure at about 0.6MPa. When the acetylene is contained, 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. The analysis can obtain a content of 82% betahistine crude product and 2 % of by-product benzene and about 15% of unreacted raw materials and other impurities, the yield is greater than 80%.

Embodiment 2

[0050] The synthesis method of betahistine provided in this example comprises the following steps: 100kg of 3-methylaminopropionitrile, 600kg of benzene, 5kg of catalyst cyclopentadienyl cobalt are put into a 1000L autoclave, and the mixture is placed under a negative pressure of 0.09MPa. , replace with high-purity nitrogen three times, pass in purified and dry acetylene gas to 0.1MPa, heat to 65°C, then continue to pass in acetylene gas, keep the temperature at 95°C, and control the pressure at about 0.8MPa, when 63kg of During acetylene, the pressure in the reactor rises sharply. At this time, the reaction is over, stop injecting acetylene gas, the pressure drops to 0.08MPa, and the temperature drops to 40°C. The content of the crude product of betahistine is 88% and 2% is analyzed except for the solvent. The by-product benzene and about 10% unreacted raw materials and other impurities, the yield is greater than 85%.

Embodiment 3

[0052] The synthetic method of betahistine provided by the present embodiment comprises the following steps: drop into 100kg 3-methylaminopropionitrile, 250kg of toluene, 2kg of catalyst a in a 1000L autoclave Cobalt and azobisisobutyronitrile are reacted in 5 times the molar amount of tetrahydrofuran), and under the negative pressure of 0.09MPa, replace with high-purity nitrogen three times, pass in purified and dry acetylene gas to 0.1MPa, and heat to 65°C , and then continue to feed acetylene gas, keep the temperature at 90°C, and control the pressure at about 0.9MPa. When 65kg of acetylene is fed into the reactor, the pressure in the reactor rises sharply. At this time, the reaction is over, stop injecting acetylene gas, and the pressure drops to 0.08MPa , the temperature was lowered to 40°C, and the analysis could obtain 96% betahistine crude product and 2% by-product benzene and 2% unreacted raw materials and other impurities except the solvent, and the yield was greater ...

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Abstract

The invention discloses a betahistine synthesis method, which comprises: carrying out a cyclization reaction on 3-methylaminopropionitrile, a solvent and a monovalent cobaltocene catalyst with acetylene in an anhydrous oxygen-free environment at a temperature of 85-95 DEG C under a certain reaction pressure to synthesize betahistine. The betahistine synthesis method provided by the invention has the advantages of simple steps, one-step synthesis of 3-methylaminopropionitrile and acetylene, low reaction temperature, good safety performance, high utilization rate of raw materials, reduction of the loss of the product in a multi-step reaction, and high product yield. Secondly, the reaction is an anhydrous reaction, so that the generation of a large amount of wastewater and alkali-containing hazardous wastes generated by taking 2vinylpyridine as a raw material can be avoided.

Description

technical field [0001] The invention belongs to the technical field of chemical production, and in particular relates to a method for synthesizing betahistine. Background technique [0002] Betahistine, also known as 2-(2-methylaminoethyl)pyridine, is very soluble in water, slightly soluble in absolute ethanol, and insoluble in propanol. Odorless, slightly bitter taste, easy to deliquescence, is an important drug for Meniere's syndrome, vascular headache and cerebral arteriosclerosis and other diseases. [0003] At present, a main synthetic method is as follows: use 2-methylpyridine as raw material, add formaldehyde to 2-hydroxyethylpyridine, then add sodium hydroxide to dehydrate to 2-vinylpyridine, and then react with methylamine hydrochloride in toluene Addition in a solvent gives betahistine hydrochloride. This synthesis method has many steps, the loss of the product is relatively serious in the preparation process, the 2-vinylpyridine waste water produced is difficult...

Claims

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Application Information

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Patent Type & Authority Applications(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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