15430-48-5Relevant academic research and scientific papers
Synthesis method of betahistine hydrochloride
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Paragraph 0031; 0032; 0035; 0036; 0041-0046; 0053; 0054, (2021/11/19)
The invention discloses a synthesis method of betahistine hydrochloride, which is a transition metal catalyst at room temperature. The basic reagent was added to a round-bottomed flask and methylamine, 2 - hydroxypyridine and an organic solvent were added under nitrogen protection. After the addition, the reaction was completed 40 - 150 °C. The reaction solution is cooled to room temperature, water is added, the transition metal catalyst is recovered by suction filtration, the filtrate is separated off, and the aqueous phase is extracted 3 times with ethyl acetate. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate, and the organic solvent was distilled off under reduced pressure. The residue was dissolved in ethanol, passed through dry hydrogen chloride and suction filtered, the filter cake was washed with a proper amount of ethanol, and dried in vacuo to yield a product. The transition metal catalyst used in the invention is a commercial reagent, has high activity, does not need to be separately prepared, and can be used repeatedly. The method has the advantages of cheap and easily available reaction raw materials, short reaction route, simple and convenient operation, environmental friendliness, good safety, high product yield and purity, easiness in industrial production and the like.
Continuous Flow Process for the Synthesis of Betahistine via Aza-Michael-Type Reaction in Water
Sun, Maolin,Yang, Jingxin,Fu, Youtian,Liang, Chaoming,Li, Hong,Yan, Guoming,Yin, Chao,Yu, Wei,Ma, Yueyue,Cheng, Ruihua,Ye, Jinxing
, p. 1160 - 1166 (2021/05/06)
A continuous flow process for the preparation of betahistine with a 90% isolated yield has been reported. 2-Vinylpyridine and saturated methylamine hydrochloride aqueous solution were used as starting materials to achieve excellent results in the silicon carbide flow reactor, which can tolerate the corrosion of chloride ions at high temperature (170 °C) and pressure (25 bar). In the continuous flow process, the product can be obtained in 2.4 min with excellent conversion (>99%) and product selectivity (94%). The throughput can reach 1.06 kg h-1, and the purity of the final product was greater than 99.9% by distillation, which were in accordance with the needs of production. This new process using environmentally friendly water as the solvent is energy-efficient, time- and cost-economic, and offers a 50% reduction in process mass intensity compared to the batch process.
Convenient Continuous Flow Synthesis of N-Methyl Secondary Amines from Alkyl Mesylates and Epoxides
Lebel, Hélène,Mathieu, Gary,Patel, Heena
, p. 2157 - 2168 (2020/11/23)
The first continuous flow process was developed to synthesize N-methyl secondary amines from alkyl mesylates and epoxides via a nucleophilic substitution using aqueous methylamine. A variety of N-methyl secondary amines were produced in good to excellent yields, including a number of bioactive compounds or their precursors. Up to 10.6 g (88% yield) of an N-methyl secondary amine was produced in 140 min process time. The amination procedure included an in-line workup, and the starting mesylate material was also produced in continuous flow from the corresponding alcohol. Finally, an in-line process combining the mesylate synthesis and nucleophilic substitution was developed.
Preparation method of orthographic optimizing betahistine hydrochloride
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, (2018/07/30)
The invention discloses a preparation method of orthographic optimizing betahistine hydrochloride, and relates to the field of drug preparation. The preparation method includes the steps: adding raw materials into a reaction bottle according to the feeding ratio (molar ratio) of 2-methylpyridine to paraformaldehyde of 1:0.57, leading in nitrogen, stirring mixture for 20 hours at the temperature of125 DEG C and at 4 barometric pressure, performing reduced pressure distillation, and collecting distillation cut at the temperature of 130-145 DEG C and under the pressure of 16mm mercury columns toobtain light-yellow oily 2-hydroxyethyl pyridine; adding the 2-hydroxyethyl pyridine into a three-opening bottle, adding sodium hydroxide according to the feeding ratio of 2-(2-Hydroxyethyl)pyridineto sodium hydroxide of 1:0.05, heating the mixture to reach 95-100 DEG C, stirring the mixture for 2 hours, removing a water layer, performing reduced pressure distillation on an oil layer, and collecting the distillation cut at the temperature of 65-70 DEG C and under the pressure of 17mm mercury columns to obtain 2-vinylpyridine. The preparation method is simple in technological process, safe tooperate and mild in reaction, production efficiency and product quality can be greatly improved, and production cost is reduced.
Aza-Michael-type addition reaction catalysed by a supported ionic liquid phase incorporating an anionic heteropoly acid
Ghasemi, Mohammad Hadi,Kowsari, Elaheh,Shafiee, Abbas
supporting information, p. 1150 - 1153 (2016/03/09)
In this work, we have obtained substituted amines under mild conditions in good yields using the Aza-Michael-type addition of various amines to vinyl compounds catalysed by a supported ionic liquid incorporating an anionic heteropoly acid. Different catalysts, including Lewis acids, Br?nsted acids and heteropoly acids were investigated in which heteropoly acids having dual Br?nsted and Lewis acid characteristics were excellent catalysts. The ionic liquid incorporating a polytungstate anion supported on magnetic diatomaceous earth as a magnetically separable heterogeneous catalyst offered the best results in terms of yield. The solid nanocatalyst was easily removed with a magnet.
