- Preparation method of dexmedetomidine hydrochloride intermediate
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The invention provides a preparation method of a dexmedetomidine intermediate. The method comprises the following steps: (1) dissolving Lewis acid in an aprotic organic solvent, cooling to below 10 DEG C, dropwise adding N-Boc-imidazole dissolved in an aprotic organic solvent, controlling the temperature below 10 DEG C, and uniformly mixing; (2) dropwise adding 1-(1-chloroethyl)-2, 3-dimethyl benzene, heating to 0-45 DEG C after dropwise adding until the reaction is complete, adding water or an inorganic acid aqueous solution for quenching, adding an aprotic organic solvent for extraction, and collecting and merging an extracted organic layer; and (3) adding a poor solvent into the organic layer, separating out a product, and drying. According to the preparation method, by optimizing the feed ratio and reaction conditions, side reactions and by-products are remarkably reduced, the production cost is remarkably reduced, the yield is high, the process is stable, and the preparation method is suitable for industrial mass production.
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Paragraph 0047-0056
(2022/01/20)
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- Preparation method of dexmedetomidine hydrochloride
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The invention discloses a preparation method of dexmedetomidine hydrochloride. The method comprises the following steps: taking 2,3-dimethyl-chloroethylbenzene as a raw material, and reacting with magnesium to prepare a Grignard reagent; carrying out addition reaction with formaldehyde to obtain 2-(2, 3-dimethylphenyl) propanol, and carrying out oxidizing through potassium dichromate to obtain 2-(2,3-dimethylphenyl) propionaldehyde; then, reacting with a methanol solution of ammonia gas to obtain imine, performing Van Leusen reaction with p-toluenesulfonylmethyl Isocyanide to obtain medetomidine; and finally, performing tartaric acid chiral resolution to obtain the dexmedetomidine hydrochloride. The method is simple in reaction condition, easy to meet and convenient to operate; and the preparation method is safe and reliable, does not involve high-risk reactions such as alkyl lithium dehydrogenation, catalytic hydrogenation and the like in the prior art, is high in safety coefficient,and has important significance in process safety of the chemical industry where safety production is taken as a first gripper and production accidents happen frequently.
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Page/Page column 6
(2020/06/20)
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- NEW PROCESSES FOR PREPARING 4-SUBSTITUTED IMIDAZOLES
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There is provided a novel process for the preparation of a compound of formula (I), (Formula (I)). There is also provided novel processes to intermediates of the compound of formula (I), as well as novel intermediates themselves.
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- PROCESS FOR THE PREPARATION OF MEDETOMIDINE
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A process of preparing Medetomidine of Formula (I) or an acid addition salt thereof, which process comprises: (i) reacting 2,3-dimethyl-methylbenzylalcohol with N-trimethylsilylimidazole, and, if desired, converting the Medetomidine to an acid addition salt thereof.
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Page/Page column 13; 15-16
(2009/05/28)
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- Method for preparing medetomidine and its salts
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The invention provides an improved, highly efficient method for preparing Medetomidine, and its salts, in particular its pharmaceutically acceptable salts. The method utilizes the high reactivity of halogenated imidazoles towards transmetalation with Grignard reagents and the subsequent reaction with 2,3-dimethylbenzaldehyde.
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Page/Page column 6
(2008/12/04)
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