113775-47-6

Usage

Side effects

This drug is most commonly given to cause sedation, so extreme sedation/lethargy for a short period of time is an expected side effect. Pale gums and lowered heart and respiratory rates can occur. Rarely, vomiting, diarrhea, and collapse may occur. When injected into the muscle, this medication can cause temporary pain at the injection site.

Mode of action

The mechanism of action of dexmedetomidine is as an Adrenergic alpha2-Agonist. Dexmedetomidine selectively binds to presynaptic alpha-2 adrenoceptors located in the brain, thereby inhibiting the release of norepinephrine from synaptic vesicles. This leads to an inhibition of postsynaptic activation of adrenoceptors, which inhibit sympathetic activity, thereby leading to sedation and anxiolysis. The analgesic effect of this agent is mediated by binding to alpha-2 adrenoceptors in the spinal cord.

References

https://www.statpearls.com/articlelibrary/viewarticle/20424/ https://pubchem.ncbi.nlm.nih.gov/compound/dexmedetomidinehttps://www.drugs.com/mtm/dexmedetomidine.html Dexmedetomidine: A Review of Its Use for Sedation in the Intensive Care Setting DOI: 10.1007/s40265-015-0419-5

InChI:InChI=1/C13H16N2/c1-9-5-4-6-12(10(9)2)11(3)13-7-14-8-15-13/h4-8,11H,1-3H3,(H,14,15)/t11-/m0/s1

Synthetic route

medetomidine (86347-14-0) → dexmedetomidine (113775-47-6)

Conditions	Yield
Stage #1: medetomidine With L-Lysine ethyl ester In ethanol at 75℃; for 3h; Stage #2: With sodium hydroxide In water at 100℃; Temperature; enantioselective reaction;	94.2%
Stage #1: medetomidine With sodium carbonate In dichloromethane at 20 - 25℃; for 0.25h; Stage #2: With L-Tartaric acid In ethanol; water at 10℃; for 1.5h; Reflux; Stage #3: With ammonium hydroxide In ethanol; water at 30 - 40℃; for 1h;	45.3%
Multi-step reaction with 2 steps 1: water; acetone / 0.5 h / 45 - 55 °C 2: water; ethanol; isopropyl alcohol / 0.2 h / 30 - 70 °C View Scheme

4-<1-(2,3-dimethylphenyl)-1-hydroxyethyl>-1-(triphenylmethyl)imidazole (176721-03-2) → dexmedetomidine (113775-47-6)

Conditions	Yield
With triethylsilane; trifluoroacetic acid In dichloromethane at -10 - 20℃;	89%
With formic acid; palladium 10% on activated carbon; ammonium formate at 120℃; for 10h;	82.8%
With triethylsilane; hydrogen; trifluoroacetic acid; palladium on activated charcoal 1.) r.t., CH2Cl2, 2.) r.t., 1 bar, 2 h, H2O; Yield given. Multistep reaction;

1H-imidazole (288-32-4) + 1-(1-chloroethyl)-2,3-dimethylbenzene → dexmedetomidine (113775-47-6)

Conditions	Yield
With iron(III) chloride at 75℃; for 0.5h; Reagent/catalyst; Temperature;	84.8%

(S)-4-(1-(2,3-dimethylphenyl)ethyl)-1-trityl-1H-imidazole → dexmedetomidine (113775-47-6)

Conditions	Yield
With hydrogenchloride In water; toluene at 80 - 84℃; for 4h;	78.6%

C13H16N2*C6H10O4 → dexmedetomidine (113775-47-6)

Conditions	Yield
In ethanol; water; isopropyl alcohol at 30 - 70℃; for 0.2h;	65%

2,3-dimethylbromobenzene (576-23-8) → dexmedetomidine (113775-47-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: 1.) magnesium, iodine / 1.) THF, reflux, 1 h, 2.) r.t., THF, 1.5 h 2: 90 percent / MnO2 / dioxane / 5 h / Heating 3: 95 percent / tetrahydrofuran / 2 h / Ambient temperature 4: 1.) trifluoroacetic acid, triethylsilane, 2.) H2 / Pd/C / 1.) r.t., CH2Cl2, 2.) r.t., 1 bar, 2 h, H2O View Scheme
Multi-step reaction with 3 steps 1.1: magnesium; iodine / tetrahydrofuran / 1 h / 65 - 70 °C 1.2: 1 h / 0 - 40 °C 2.1: methylmagnesium bromide / tetrahydrofuran; 2-methyltetrahydrofuran / 2 h / 0 - 20 °C 3.1: formic acid; ammonium formate; palladium 10% on activated carbon / 10 h / 120 °C View Scheme
Multi-step reaction with 4 steps 1.1: ethylene dibromide; magnesium / tetrahydrofuran / 1 h / 40 - 65 °C 1.2: 2 h / -5 - 0 °C 1.3: 3 h / 30 °C 2.1: tetrahydrofuran / 2 h / 0.4 - 65 °C 3.1: toluene-4-sulfonic acid / toluene / 2 h / 0.11 °C / Dean-Stark 4.1: (R)-1-[(SP)-2-(diphenylphosphino)ferrocenyl]ethyl-di-tert-butylphosphine; bis(norbornadiene)rhodium(l)tetrafluoroborate; hydrogen / methanol / 5 h / 40 - 45 °C / 2250.23 - 7500.75 Torr View Scheme

4-<(2,3-dimethylphenyl)carbonyl>-1-(triphenylmethyl)imidazole (176721-02-1) → dexmedetomidine (113775-47-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent / tetrahydrofuran / 2 h / Ambient temperature 2: 1.) trifluoroacetic acid, triethylsilane, 2.) H2 / Pd/C / 1.) r.t., CH2Cl2, 2.) r.t., 1 bar, 2 h, H2O View Scheme

4-<(2,3-dimethylphenyl)hydroxymethyl>-1-(triphenylmethyl)imidazole (176721-01-0) → dexmedetomidine (113775-47-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 90 percent / MnO2 / dioxane / 5 h / Heating 2: 95 percent / tetrahydrofuran / 2 h / Ambient temperature 3: 1.) trifluoroacetic acid, triethylsilane, 2.) H2 / Pd/C / 1.) r.t., CH2Cl2, 2.) r.t., 1 bar, 2 h, H2O View Scheme

(S)-dexmedetomidine-L-(+)-tartrate (176721-04-3) → dexmedetomidine (113775-47-6)

Conditions	Yield
With sodium hydrogencarbonate	12.16 g

C4H6O5*C13H16N2 → dexmedetomidine (113775-47-6)

Conditions	Yield
With sodium hydroxide In dichloromethane pH=> 12;	65 g

1-(1-chloroethyl)-2,3-dimethylbenzene → dexmedetomidine (113775-47-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: titanium tetrachloride; triethylamine / dichloromethane / 5 h / -3 - 20 °C 2.1: sodium carbonate / dichloromethane / 0.25 h / 20 - 25 °C 2.2: 1.5 h / 10 °C / Reflux 2.3: 1 h / 30 - 40 °C View Scheme

1-(2,3-dimethyl-phenyl)-ethanone (2142-71-4) → dexmedetomidine (113775-47-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: tetrabutyl-ammonium chloride; lanthanum(III) chloride; SeCl3 / diethyl ether; tetrahydrofuran / 0.5 h / 20 °C / Schlenk technique; Inert atmosphere 1.2: 3 h / 0 - 20 °C 2.1: triethylsilane; trifluoroacetic acid / dichloromethane / -10 - 20 °C View Scheme

medetomidine (86347-14-0) → dexmedetomidine (113775-47-6) + levomedetomidine

Conditions	Yield
Stage #1: medetomidine With L-lysine In ethanol at 75℃; for 12h; Stage #2: With sodium hydroxide In water at 100℃; Overall yield = 61.7 %; Overall yield = 13.3 g; enantioselective reaction;	A n/a B n/a
With Chiralcel OJ-3R In acetonitrile at 25℃; pH=8; Reagent/catalyst; Resolution of racemate;

1H-imidazole (288-32-4) + 1-(1-chloroethyl)-2,3-dimethylbenzene → dexmedetomidine (113775-47-6) + levomedetomidine

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; 1-butyl-3-methylimidazolium Tetrafluoroborate at 90℃; for 0.5h; Temperature; Reagent/catalyst; Inert atmosphere; Overall yield = 81.1 %; Overall yield = 16.9 g;	A n/a B n/a
With [1,1'-bis(diphenylphosphino)ferrocene]nickel(II) chloride; potassium carbonate; zinc In N,N-dimethyl-formamide at 70℃; for 5h; Reagent/catalyst; Temperature; Inert atmosphere; Overall yield = 89.5 %; Overall yield = 17.9 g; Optical yield = 90.61 %ee;

C20H19ClN2O → dexmedetomidine (113775-47-6)

Conditions	Yield
With phosphoric acid at 23℃; for 48h; pH=6.5; Enzymatic reaction;	18.2 g

1H-imidazole (288-32-4) + 1-(2,3-dimethylphenyl)ethyl trifluoromethanesulfonate → dexmedetomidine (113775-47-6) + levomedetomidine

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; N-butylpyridinium tetrafluoroborate at 70℃; for 0.5h; Temperature; Reagent/catalyst; Inert atmosphere; Overall yield = 84.7 %; Overall yield = 17.6 g; Optical yield = 79.89 %ee;

1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2) → dexmedetomidine (113775-47-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: triethylamine / chloroform / 2 h / 20 - 26 °C / Inert atmosphere 2: bis(norbornadiene)rhodium(l)tetrafluoroborate; hydrogen; (2R)-1-[(1R)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-[bis[4-(trifluoromethyl)phenyl]phosphino]ferrocene / dichloromethane / 24 h / 25 °C / 6000.6 Torr 3: hydrogenchloride / toluene; water / 4 h / 80 - 84 °C View Scheme
Multi-step reaction with 3 steps 1: triethylamine / chloroform / 2 h / 20 - 26 °C / Inert atmosphere 2: bis(norbornadiene)rhodium(l)tetrafluoroborate; hydrogen; (2S)-1-[(1S)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(diphenylphosphino)ferrocene / dichloromethane / 3 h / 25 °C / 6000.6 Torr 3: hydrogenchloride / toluene; water / 4 h / 80 - 84 °C View Scheme

4-(1-(2,3-dimethylphenyl)vinyl)-1-trityl-1H-imidazole → dexmedetomidine (113775-47-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: bis(norbornadiene)rhodium(l)tetrafluoroborate; hydrogen; (2R)-1-[(1R)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-[bis[4-(trifluoromethyl)phenyl]phosphino]ferrocene / dichloromethane / 24 h / 25 °C / 6000.6 Torr 2: hydrogenchloride / toluene; water / 4 h / 80 - 84 °C View Scheme
Multi-step reaction with 2 steps 1: bis(norbornadiene)rhodium(l)tetrafluoroborate; hydrogen; (2S)-1-[(1S)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(diphenylphosphino)ferrocene / dichloromethane / 3 h / 25 °C / 6000.6 Torr 2: hydrogenchloride / toluene; water / 4 h / 80 - 84 °C View Scheme

4-(2,3-dimethylbenzoyl)-1H-imidazole → dexmedetomidine (113775-47-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: tetrahydrofuran / 2 h / 0.4 - 65 °C 2: toluene-4-sulfonic acid / toluene / 2 h / 0.11 °C / Dean-Stark 3: (R)-1-[(SP)-2-(diphenylphosphino)ferrocenyl]ethyl-di-tert-butylphosphine; bis(norbornadiene)rhodium(l)tetrafluoroborate; hydrogen / methanol / 5 h / 40 - 45 °C / 2250.23 - 7500.75 Torr View Scheme

1-(2,3-dimethylphenyl)-1-(1H-imidazol-4-yl)ethanol → dexmedetomidine (113775-47-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / toluene / 2 h / 0.11 °C / Dean-Stark 2: (R)-1-[(SP)-2-(diphenylphosphino)ferrocenyl]ethyl-di-tert-butylphosphine; bis(norbornadiene)rhodium(l)tetrafluoroborate; hydrogen / methanol / 5 h / 40 - 45 °C / 2250.23 - 7500.75 Torr View Scheme

1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2) → dexmedetomidine (113775-47-6) + levomedetomidine

Conditions	Yield
With bis(norbornadiene)rhodium(l)tetrafluoroborate; (R)-1-[(SP)-2-(diphenylphosphino)ferrocenyl]ethyl-di-tert-butylphosphine; hydrogen In methanol at 40 - 45℃; under 2250.23 - 7500.75 Torr; for 5h; Optical yield = 79.3 percent ee;

dexmedetomidine (113775-47-6) → dexmedetomidine hydrochloride

Conditions	Yield
With hydrogenchloride In ethanol; ethyl acetate at 20℃; for 1h;	92.5%
With hydrogenchloride In ethanol; water; isopropyl alcohol at 35 - 50℃;	90%

L-Tartaric acid (87-69-4) + dexmedetomidine (113775-47-6) → (S)-dexmedetomidine-L-(+)-tartaric acid salt

Conditions	Yield
In ethanol; isopropyl alcohol at 20℃; Reflux;	77.1%

dexmedetomidine (113775-47-6) → Rezatomidine (847829-38-3)

Conditions	Yield
With sodium hydrogencarbonate; phenylcarbonochloridothioate In tetrahydrofuran; water at 20℃; for 4h;	53%
With sodium hydrogencarbonate; phenylcarbonochloridothioate In tetrahydrofuran; water at 20℃; for 4h;	53%

L-Tartaric acid (87-69-4) + dexmedetomidine (113775-47-6) → (S)-dexmedetomidine-L-(+)-tartrate (176721-04-3)

Conditions	Yield
In ethanol at 65℃; for 2h; Temperature;	47.3%

dexmedetomidine (113775-47-6) + p-toluenesulfonyl chloride (98-59-9) → (+)-(S)-4-<1-(2,3-dimethylphenyl)ethyl>-1-tosyl-1H-imidazole

Conditions	Yield
With triethylamine In dichloromethane for 2.5h; Ambient temperature;	31.1%

dexmedetomidine (113775-47-6) → (S)-4-[1-(2,3-dimethylphenyl)ethyl]-3H-imidazole hydrobromide (1391972-96-5)

Conditions	Yield
With hydrogen bromide Dean-Stark;

dexmedetomidine (113775-47-6) → (S)-4-[1-(2,3-dimethylphenyl)ethyl]-3H-imidazole hydroiodide

Conditions	Yield
With hydrogen iodide Dean-Stark;

oxalic acid (144-62-7) + dexmedetomidine (113775-47-6) → (S)-4-[1-(2,3-dimethylphenyl)ethyl]-3H-imidazole oxalate

Conditions	Yield
In ethanol

ethyl iodide (75-03-6) + dexmedetomidine (113775-47-6) → C15H20N2 + C15H20N2

Conditions	Yield
With sodium hydride In tetrahydrofuran at 0 - 50℃; for 4h; Temperature; Solvent; Reagent/catalyst;	A 200 mg B 400 mg

Upstream product

• 288-32-4 1H-imidazole 
• 60907-88-2 1-(1-chloroethyl)-2,3-dimethylbenzene 
• 1021949-47-2 1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene 
• 86347-14-0 medetomidine 
• 2142-71-4 1-(2,3-dimethyl-phenyl)-ethanone 
• 176721-04-3 (S)-dexmedetomidine-L-(+)-tartrate 
• 176721-01-0 4-<(2,3-dimethylphenyl)hydroxymethyl>-1-(triphenylmethyl)imidazole 
• 176721-02-1 4-<(2,3-dimethylphenyl)carbonyl>-1-(triphenylmethyl)imidazole 
• 576-23-8 2,3-dimethylbromobenzene 
• 176721-03-2 4-<1-(2,3-dimethylphenyl)-1-hydroxyethyl>-1-(triphenylmethyl)imidazole 

Downstream Products

• 176721-04-3 (S)-dexmedetomidine-L-(+)-tartrate 
• 1391972-96-5 (S)-4-[1-(2,3-dimethylphenyl)ethyl]-3H-imidazole hydrobromide 
• 847829-38-3 Rezatomidine 

Relevant academic research and scientific papers

Development and validation of a chiral LC-MS method for the enantiomeric resolution of (+) and (?)-medetomidine in equine plasma by using polysaccharide-based chiral stationary phases

The detection and separation of medetomidine enantiomers from the complex biological matrices poses a great analytical challenge, especially in the field of forensic toxicology and pharmacology. Couple of researchers reported resolution of medetomidine using protein-based chiral columns, but the reported method is quiet challenging and tedious to be employed for routine analysis. This research paper reported a method that enables the enantio-separation of medetomidine by using polysaccharide cellulose chiral column. The use of chiralcel OJ-3R column was found to have the highest potential for successful chiral resolution. Ammonium hydrogen carbonate was the ideal buffer salt for chiral liquid chromatography (LC) with electrospray ionization (ESI)+ mass spectrometry (MS) detection for the successful separation and detection of racemic compound. The method was linear over the range of 0 to 20 ng/mL in equine plasma and the inter-day precisions of levomedetomidine, dexmedetomidine were 1.36% and 1.89%, respectively. The accuracy of levomedetomidine was in the range of 99.25% to 101.57% and that for dexmedetomidine was 99.17% to 100.99%. The limits of quantification for both isomers were 0.2 ng/mL. Recovery and matrix effect on the analytes were also evaluated. Under the optimized conditions, the validated method can be adapted for the identification and resolution of the medetomidine enantiomers in different matrices used for drug testing and analysis.

Efficient synthesis of (S)-4(5)-[1-(2,3-dimethylphenyl) ethyl]imidazole tartrate, the potent α2 adrenoceptor agonist dexmedetomidine

(S,R)-4(5)-[1-(2,3-dimethylphenyl)ethyl]imidazole 5 is prepared in 41% yield, by a new reliable method from readily available starting materials. The separation of the enantiomers proceeds through the selective crystallisation of the (+)-tartrate of the (S) enantiomer 6 in the presence of the (R) enantiomer free base.

Synthesis method of dexmedetomidine

The invention discloses a synthesis method of dexmedetomidine, which comprises the following steps: by taking (2,3-dimethylphenyl)(1H-imidazol-5-yl)methanone (I) as a starting material, conducting reacting with ethyl chloroformate to obtain 4-(2,3-dimethylbenzoyl)-1H-imidazol-1-ethyl formate (II), reacting with formaldehyde to obtain ethyl 4-(1-(2, 3-dimethylbenzoyl)-1H-imidazole-1-formate (II), and conducting reacting with formaldehyde to obtain ethyl 4-(1-(2,3-dimethylphenyl)vinyl)-1H-imidazol-1-formate (III), conducting chiral catalytic reduction to obtain ethyl (S)-4-(1-(2,3-dimethylphenyl)ethyl)-1H-imidazol-1-formate (III), and conducting deprotection to obtain dexmedetomidine. The synthetic method is short in synthetic route, easy to operate and high in yield.

METHOD FOR PREPARING DEXMEDETOMIDINE

The present invention relates to a method for preparing dexmedetomidine having the following formula (I): or a pharmaceutically acceptable salt and/or solvate thereof, comprising the following successive steps: a) asymmetric hydrogenation of a methylene derivative of the following formula (II): in order to obtain dexmedetomidine, and b) optionally salifying and/or solvating dexmedetomidine in order to obtain a pharmaceutically acceptable salt and/or solvate of dexmedetomidine, wherein the methylene derivative of formula (II) is prepared from a halide of the following formula (V), in which Hal2 represents a halogen atom such as Br, and a cyanoimidazole of the following formula (VI):. The present invention relates also to methods for preparing synthesis intermediates of dexmedetomidine from the halide of formula (V) and the cyanoimidazole of formula (VI), these synthesis intermediates being the methylene derivative of formula (II), an alcohol of the following formula (III), and a ketone of the following formula (IV):.

METHOD FOR PRODUCING IMIDAZOLE DERIVATIVE

PROBLEM TO BE SOLVED: To provide a novel method for producing an optically active imidazole compound useful as a pharmaceutical. SOLUTION: A production method includes the steps for making a compound represented by formula (3) react with hydrogen gas in the presence of an optically active metal complex catalyst, to obtain a compound represented by formula (4) with high yield and high selectivity (in the formula, R1 is an amino protecting group, and * is an asymmetric carbon atom). SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT

Intermediate for preparing medetomidine and its preparation method and use

The invention provides an intermediate for preparing medetomidine. The intermediate is a compound shown in the formula (I). The invention also provides a preparation method of the intermediate, and ause of the intermediate in the preparation of medetomidine. The compound shown in the formula (I) is used for preparation of medetomidine so that the raw material is cheap and easy to obtain, synthesis processes are simple, the reaction cycle is short, the environmental pollution is avoided, operation is simple, the harsh reaction conditions are avoided, the operation and post-treatment are simple, the yield and the product purity are high, the intermediate in each step is a solid and is easy to purify, a production cost is low, and the intermediate is suitable for industrial large-scale production and conforms to the principle of green chemistry.

Method for synthesizing dexmedetomidine hydrochloride intermediate

The invention discloses a method for synthesizing a dexmedetomidine hydrochloride intermediate. The synthesis method comprises the step that 1-(1-trifluoromethanesulfonate)ethyl-2,3-dimethylbenzene and imidazole are subjected to stirring reacting in ionic liquid in the presence of alkali and [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride to obtain the dexmedetomidine hydrochloride intermediate 4-[1-(2,3-dimethylbenzene)ethyl]-1H-imidazole. The method is short in reacting time and high in product production efficiency and yield and has the good selectivity on a target (S)-isomer.

Preparation process of dexmedetomidine hydrochloride for ICU (intensive care unit) sedation and analgesia

The invention discloses a preparation process of dexmedetomidine hydrochloride for ICU (intensive care unit) sedation and analgesia. The preparation process includes the steps: first, stirring and reacting 1-(1-halogenated ethyl)-2, 3-dimethyl benzene and imidazole in ionic liquid under catalysis of ferric trichloride to obtain 4-[1-(2, 3-dimethyl phenyl) ethyl]-1H-imidazole; second, refluxing the 4-[1-(2, 3-dimethyl phenyl) ethyl]-1H-imidazole obtained in the first step and L-(+)-tartaric acid in absolute ethyl alcohol, and performing standing, cooling and suction filtration to obtain dexmedetomidine tartrate; third, stirring the dexmedetomidine tartrate in sodium hydroxide aqueous solution, extracting methylene dichloride, concentrating the solution, stirring the solution in saturated hydrochloric acid methanol solution to obtain the dexmedetomidine hydrochloride. The method is short in reaction time, high in yield, milder in condition and suitable for industrial popularization.

Synthetic method of dexmedetomidine hydrochloride intermediate

The invention discloses a synthetic method of a dexmedetomidine hydrochloride intermediate. The synthetic method comprises the following step: carrying out contact reaction on 1-(1-haloethyl)-2,3-dimethylbenzene and imidazole in ionic liquid in the presence of alkali and [1,1'-bis(diphenylphosphino) ferrocene] palladium dichloride to obtain the dexmedetomidine hydrochloride intermediate 4-[1-(2,3-dimethyl phenyl) ethyl]-1H-imidazole. The method is short in reaction time and high in yield, and has good selectivity for a target (S)-isomer.

A hydrochloride right tablet the onamot decides intermediate preparation process (by machine translation)

The invention discloses a right hydrochloride tablet the onamot decides intermediate preparation process, the preparation process includes: will be 1 - (1 - halogenated ethyl) - 2, 3 - dimethylphenyl and imidazole and alkali and NiCl2 (Dppf) added to the organic solvent in the obtained by stirring reaction the temperature of the hydrochloric acid right tablet the onamot decides intermediate 4 - [1 - (2, 3 - dimethyl phenyl) ethyl] - 1H - imidazole. According to the present invention to provide a preparation process of a hydrochloric acid preparation of the right tablet the onamot decides intermediate 4 - [1 - (2, 3 - dimethyl phenyl) ethyl] - 1H - imidazole high yield and the target (S)- isomer has good selectivity. (by machine translation)