Preparation method of medetomidine

A technology of medetomidine and trimethylsilimidazole, which is applied in the field of drug synthesis, can solve the problems of difficult recycling, large amount of catalyst, and difficult recovery of solvents, and achieve the effect of reducing solvent loss and emission

Pending Publication Date: 2022-01-07
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] The object of the present invention is to, based on the present situation of prior art, in order to solve present medetomidine synthesis process, the difficult problem that c

Method used

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  • Preparation method of medetomidine
  • Preparation method of medetomidine
  • Preparation method of medetomidine

Examples

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Example Embodiment

[0021] Example 1

[0022]

[0023] The installation of a mechanical stirrer, internal thermometer, dropping funnel, the reaction flask has invested trifluoromethylphenyl 100g, sulfate - 1.68 g of silica gel (Ref. Tetrahedron Letters, 2007,48,3783-3787 Preparation method), the internal temperature drop to -10 deg.] C, and then added dropwise a solution of trimethylsilyl imidazole 16.83gN- trifluoromethyl and 100g of toluene at this temperature, stirred for 30 min after addition; was slowly added dropwise a 16.87g1- (1- chloroethyl) trifluoromethyl-2,3-xylene and 136g of toluene solution, in this case within the control temperature -10 ~ -5 ℃, after completion of the dropwise addition, stirring was continued for 4 hours at this temperature, and thin layer chromatography (TLC ) monitoring the reaction progress; after the completion of the reaction, vacuum filtration, and the filter cake was rinsed to 10g trifluoromethylphenyl. The filter cake (catalyst) was dried in vacuo and then ...

Example Embodiment

[0026] Example 2

[0027]

[0028] The installation of a mechanical stirrer, internal thermometer, dropping funnel, the reaction flask has invested trifluoromethylphenyl 100g, Amberlyst 15 cation exchange resin 2.81 g, the inner temperature was lowered to -5 deg.] C, and then added dropwise at this temperature by a 16.83 gN- trimethylsilyl imidazole and trifluoroacetic 100g of toluene solution after complete addition stirring 30min. Was slowly dropwise added 16.87g 1- (1- chloroethyl) -2,3-xylene and 136g of toluene solution of trifluoromethyl, in this case within the control temperature -5 ~ 0 ℃, after completion of the dropwise addition, this stirring was continued at temperature for 7 hours, and thin layer chromatography (TLC) monitoring the reaction progress; after the reaction is completed, vacuum filtration, and rinsed in a 10g trifluoromethylphenyl filter cake (catalyst) Natural dry spare ; the filtrate was heated to 50 deg.] C and incubated for 1 hour, allowed to cool wa...

Example Embodiment

[0030] Example 3

[0031]

[0032] To the reaction bottle mounted, the built-in temperature meter, the drip funnel, the HZSM-5 molecular sieve 3G, the temperature dropped to 0 ° C, then at this temperature, 15.83 GN-Trimethium The solution of the base silicon imidazole and 100 g chlorobenzene is added after the addition is 30 min; slowly added a solution of 16.87 g 1- (1-chlorthyl) -2,3-xylene and 136 g of chlorobenzene, at this time When the temperature did not exceed 5 ° C, stirring was continued for 8 hours at this temperature, and the reaction process was monitored by a thin layer chromatography (TLC); after the reaction was completed, the filtration was filtered under reduced pressure, and filtered with 10 g of chlorobenzene Pie, filter cake (catalyst) naturally drying back with a small amount of diethyl ether; heating the filtrate to 50 ° C and holding for 1 hour, naturally cooled, 30 ml × 3, saturated saline 30 ml of water, anhydrous sodium sulfate Dry reduced pressure dist...

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Abstract

The invention belongs to the technical field of medicine synthesis, and particularly relates to a preparation method of medetomidine. According to the method, 1-(1-chloroethyl)-2, 3-dimethyl benzene and N-trimethylsilylimidazole are used as raw materials, solid acid is used as a catalyst, and reaction is carried out in an aromatic solvent to prepare medetomidine. According to the method, the catalyst is small in dosage and can be recycled, the solvent recycling efficiency is high, and generation of chemical waste can be effectively reduced.

Description

technical field [0001] The invention belongs to the technical field of medicine synthesis, and in particular relates to a preparation method of medetomidine. Background technique [0002] The prior art discloses that the chemical name of dexmedetomidine hydrochloride is 4-[(1S)-1-(2,3-dimethylphenyl)ethyl]-1H imidazole hydrochloride, which is a novel alpha - Adrenoceptor agonist, first launched in the United States in 2000. Studies have shown that dexmedetomidine hydrochloride can be used for sedation of patients who start intubation and use ventilators during intensive care treatment. The sedation produced by it is a natural sleep state similar to human non-eye movement sleep and easy to wake up. There are great advantages in application. [0003] Studies have shown that dexmedetomidine hydrochloride is an S-type dextrorotatory optical isomer; the current mainstream preparation process is to first synthesize its racemic form of medetomidine, and then split it and form a s...

Claims

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Application Information

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IPC IPC(8): C07D233/58
CPCC07D233/58
Inventor 张伟江凡李英俏李航
Owner FUDAN UNIV
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