- A novel and facile route for the synthesis of medetomidine as the α2-adrenoceptor agonist
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Abstract: We report here a novel and facile method for the synthesis of (±)-4(5)-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole (medetomidine) in a good yield in five steps. The method involves Wittig olefination of the phenylimidazolylketones, followed by a hydrogenation. We demonstrate that the Wittig alkenylation reaction provides a convenient step for the synthesis of medetomidine without requiring methylation and dehydration steps, which are problematic processes in the previous methods. Graphical Abstract: Novel route for the synthesis of medetomidine.[Figure not available: see fulltext.].
- Kaboudin, Babak,Haghighat, Hamideh,Aieni, Samira,Behrouzi, Leila,Kazemi, Foad,Kato, Jun-ya,Aoyama, Hiroshi,Yokomatsu, Tsutomu
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- Expedient synthesis of 4(5)-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole, the α2-adrenergic agonist medetomidine
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(+)-4(5)-[1-(2,3-Dimethylphenyl)ethyl]-1H-imidazole hydrochloride (5) is prepared in three steps in 79% overall yield from 1-(N,N-dimethylsulfamoyl)imidazole by bis-protection, regioselective lithiation followed by an efficient tandem addition-reduction of the resulting 2,3-dimethylbenzoyl chloride adduct with lithium/ammonia/ammonium chloride.
- Kudzma,Turnbull Jr.
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- Preparation method of high-purity dexmedetomidine hydrochloride
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The invention discloses a preparation method of high-purity dexmedetomidine hydrochloride, which comprises the following steps: by taking 1-(1-chloroethyl)-2, 3-dimethyl benzene and N-trimethylsilylimidazole as reaction raw materials, carrying out Friedel-Crafts alkylation reaction under the catalysis of an aprotic organic solvent and lewis acid, recrystallizing the obtained post-treated oil by using a specific solvent to obtain medetomidine solid, splitting by chiral acid, free of alkali and salt forming, and preparing the high-purity dexmedetomidine hydrochloride. According to the dexmedetomidine hydrochloride prepared by the preparation method disclosed by the invention, the splitting and refining times can be effectively reduced, the chemical purity and optical purity of the obtained dexmedetomidine hydrochloride can reach 100%, and the total yield is relatively high; and moreover, main starting materials are conventional industrial commodities, so that the preparation method is suitable for industrial production and has relatively high industrial application value.
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Paragraph 0054-0056; 0061-0062
(2021/06/22)
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- Method for synthesizing dexmedetomidine hydrochloride
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The invention belongs to the technical field of drug preparation, and particularly relates to a method for synthesizing dexmedetomidine hydrochloride. The method for synthesizing dexmedetomidine hydrochloride comprises the steps that reaction of 2,3-dimethylbenzoyl chloride and 1-N,N-dimethyl sulfonyl-2-(tert-butyldimethylsily)-5-(2,3-dimethyl benzoyl) imidazole is adopted, reflux is carried out to remove a protecting group under the action of hydrochloric acid, intermediate 4(5)-(2,3-dimethyl benzoyl) imidazole is obtained, lastly, reduction is carried out to obtain medetomidine under the action of monomethylamine, dexmedetomidine is obtained through the resolution of medetomidine under the action of tartaric acid, and lastly, dexmedetomidine is salified with hydrochloric acid to obtain dexmedetomidine hydrochloride. Compared with the prior art, the method for synthesizing dexmedetomidine hydrochloride has the advantages that a synthetic route is shorter, the operation is easy, and astarting material is easy to obtain.
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- Industrial preparation method of dexmedetomidine hydrochloride
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The invention discloses an industrial preparation method of dexmedetomidine hydrochloride, and belongs to the field of medicines. The method comprises the following steps: directly carrying out a Friedel-Crafts alkylation reaction on initial raw materials comprising 1-(2,3-dimethylphenyl)ethanol not subjected to a chlorination (thionyl chloride) reaction and protected imidazole under the catalysis of a Lewis acid to obtain racemic dexmedetomidine, carrying out pre-resolution purification on the racemic dexmedetomidine through a chiral acid, carrying out chiral acid resolution and alkali dissociation, and adding a hydrochloric acid organic solvent to form a salt in order to obtain the dexmedetomidine hydrochloride. The method avoids use of the toxic and corrosive regent thionyl chloride, allows the above product with high chiral and chemical purity to be obtained and the yield to be high, and is suitable for industrial production.
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Paragraph 0019
(2017/08/28)
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- PROCESSES FOR THE PREPARATION OF COMPOUNDS, SUCH AS 3-ARYLBUTANALS, USEFUL IN THE SYNTHESIS OF MEDETOMIDINE
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There is provided a process for the preparation of a compound of formula (I) as defined herein, wherein said process comprises reacting a compound of formula (II) as defined s herein with one or more suitable Vilsmeier reagent.
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- METHOD FOR THE PREPARATION OF MEDETOMIDINE
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The invention discloses a method for the preparation of medetomidine starting from 1-bromo 2,3-dimethylbenzene and aceton.
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Page/Page column 28
(2013/02/28)
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- METHOD FOR THE PREPARATION OF MEDETOMIDINE WITH CHLOROACETONE
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The invention discloses a method for the preparation of medetomidine starting from 1-bromo 2,3-dimethylbenzene and chloroacetone.
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Page/Page column 26
(2013/02/28)
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