1021949-47-2

Basic information

• Product Name: 5-[1-(2,3-DiMethylphenyl)ethenyl]iMidazole
• Synonyms: 5-[1-(2,3-DiMethylphenyl)ethenyl]iMidazole;5-[1-(2,3-Dimethylphenyl)ethenyl]-1H-imidazole;4-[1-(2,3-DiMethyl-phenyl)-vinyl]-1H-iMidazole;5-(1-(2,3-DiMethylphenyl)vinyl)-1H-iMidazole;Medetomidine Impurity 3;5-[1-(2,3-Dimethylephenyl]-1H-imidazole
• CAS NO: 1021949-47-2
• Molecular Formula: C₁₃H₁₄N₂
• Molecular Weight: 198
• Mol File: 1021949-47-2.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 393.2±11.0 °C(Predicted)
• Appearance: /
• Density: 1.066
• Storage Temp.: 2-8°C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 13.68±0.10(Predicted)
• CAS DataBase Reference: 5-[1-(2,3-DiMethylphenyl)ethenyl]iMidazole(CAS DataBase Reference)
• NIST Chemistry Reference: 5-[1-(2,3-DiMethylphenyl)ethenyl]iMidazole(1021949-47-2)
• EPA Substance Registry System: 5-[1-(2,3-DiMethylphenyl)ethenyl]iMidazole(1021949-47-2)

Safety Data

• Hazardous Substances Data: 1021949-47-2(Hazardous Substances Data)

Usage

Uses

5-[1-(2,3-Dimethylphenyl)ethenyl]-1H-imidazole is an impurity of Dexmedetomidine (D229000), an α2-Adrenergic agonist; (+)-isomer of Medetomidine; sedative; analgesic.

InChI:InChI=1S/C13H14N2/c1-9-5-4-6-12(10(9)2)11(3)13-7-14-8-15-13/h4-8H,3H2,1-2H3,(H,14,15)

Synthetic route

1-(2,3-dimethylphenyl)-1-(1H-imidazol-4-yl)ethanol → 1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2)

Conditions	Yield
With toluene-4-sulfonic acid In toluene at 0.11℃; for 2h; Reagent/catalyst; Solvent; Temperature; Dean-Stark;	100%

4-(2,3-dimethylbenzoyl)-1H-imidazole + Methyltriphenylphosphonium bromide (1779-49-3) → 1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2)

Conditions	Yield
With potassium tert-butylate In tetrahydrofuran at 20 - 25℃; for 18h; Wittig Olefination;	94%

(1-trityl-1H-imidazol-4-yl)boronic acid + C10H11Br → 1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2)

Conditions	Yield
Stage #1: (1-trityl-1H-imidazol-4-yl)boronic acid; C10H11Br With tris-(dibenzylideneacetone)dipalladium(0); sodium phosphate In 5,5-dimethyl-1,3-cyclohexadiene; water at 105℃; Inert atmosphere; Stage #2: With toluene-4-sulfonic acid In tetrahydrofuran at 20 - 65℃; for 1.5h; Reagent/catalyst; Solvent; Temperature;	74.9%

5-[1-(2,3-dimethylphenyl)vinyl]-1H-imidazole hydrochloride → 1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2)

Conditions	Yield
With sodium hydroxide; water at 0 - 25℃; for 1 - 1.5h;

4-<(2,3-dimethylphenyl)carbonyl>-1-(triphenylmethyl)imidazole (176721-02-1) → 1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: n-butyllithium / hexane; tetrahydrofuran / 1 h / 0 °C / Inert atmosphere 1.2: 24 h / 0 °C / Inert atmosphere 2.1: trifluoroacetic acid; water / 12 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: potassium tert-butylate / tetrahydrofuran / 0.5 h / 0 °C 1.2: 4 h / 20 °C 2.1: hydrogenchloride / dichloromethane View Scheme

4-(1-(2,3-dimethylphenyl)vinyl)-1-trityl-1H-imidazole → 1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2)

Conditions	Yield
With water; trifluoroacetic acid at 20℃; for 12h;
With hydrogenchloride In dichloromethane	19.5 g

4-<(2,3-dimethylphenyl)hydroxymethyl>-1-(triphenylmethyl)imidazole (176721-01-0) → 1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: manganese(IV) oxide / 1,4-dioxane / Reflux 2.1: n-butyllithium / hexane; tetrahydrofuran / 1 h / 0 °C / Inert atmosphere 2.2: 24 h / 0 °C / Inert atmosphere 3.1: trifluoroacetic acid; water / 12 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: manganese(IV) oxide / 1,4-dioxane / 5 h / Reflux 2: tetrahydrofuran; diethyl ether / 2 h / 0 - 20 °C 3: triethylsilane; trifluoroacetic acid / dichloromethane / 4 h / -10 °C View Scheme
Multi-step reaction with 3 steps 1.1: manganese(IV) oxide / 1,4-dioxane / 3 h / Reflux 2.1: potassium tert-butylate / tetrahydrofuran / 0.5 h / 0 °C 2.2: 4 h / 20 °C 3.1: hydrogenchloride / dichloromethane View Scheme

2,3-dimethylbromobenzene (576-23-8) → 1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: magnesium / tetrahydrofuran 1.2: 0 °C 2.1: manganese(IV) oxide / 1,4-dioxane / Reflux 3.1: n-butyllithium / hexane; tetrahydrofuran / 1 h / 0 °C / Inert atmosphere 3.2: 24 h / 0 °C / Inert atmosphere 4.1: trifluoroacetic acid; water / 12 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: magnesium; iodine / tetrahydrofuran / 1 h / Reflux 1.2: 1.5 h / 0 - 20 °C 2.1: manganese(IV) oxide / 1,4-dioxane / 5 h / Reflux 3.1: tetrahydrofuran; diethyl ether / 2 h / 0 - 20 °C 4.1: triethylsilane; trifluoroacetic acid / dichloromethane / 4 h / -10 °C View Scheme
Multi-step reaction with 4 steps 1.1: (bis(tricyclohexyl)phosphine)palladium(II) dichloride; copper(l) iodide; N-ethyl-N,N-diisopropylamine / 2-methyltetrahydrofuran / 30 °C / Inert atmosphere 2.1: caesium carbonate / ethanol / 30 °C / Inert atmosphere 3.1: hydrogen bromide; acetic acid / dichloromethane / 0 - 10 °C / Inert atmosphere 4.1: sodium phosphate; tris-(dibenzylideneacetone)dipalladium(0) / 5,5-dimethyl-1,3-cyclohexadiene; water / 105 °C / Inert atmosphere 4.2: 1.5 h / 20 - 65 °C View Scheme
Multi-step reaction with 4 steps 1.1: magnesium; iodine / tetrahydrofuran / 1.5 h / 70 °C / Inert atmosphere 1.2: -5 - 20 °C / Inert atmosphere 2.1: manganese(IV) oxide / 1,4-dioxane / 3 h / Reflux 3.1: potassium tert-butylate / tetrahydrofuran / 0.5 h / 0 °C 3.2: 4 h / 20 °C 4.1: hydrogenchloride / dichloromethane View Scheme
Multi-step reaction with 3 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 / Large scale 3.1: toluene-4-sulfonic acid / toluene / 2 h / 0.11 °C / Dean-Stark View Scheme

(2,3-dimethylphenyl)(1H-imidazol-4-yl)methanol → 1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: Dess-Martin periodane; magnesium sulfate / dichloromethane / 12 h / 20 - 30 °C 2: potassium tert-butylate / tetrahydrofuran / 18 h / 20 - 25 °C View Scheme

2,3-dimethylbenzaldehyde (5779-93-1) → 1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: magnesium; iodine / tetrahydrofuran / 35 - 65 °C / Inert atmosphere 1.2: 6 h / 20 - 25 °C 2.1: Dess-Martin periodane; magnesium sulfate / dichloromethane / 12 h / 20 - 30 °C 3.1: potassium tert-butylate / tetrahydrofuran / 18 h / 20 - 25 °C View Scheme

4-<1-(2,3-dimethylphenyl)-1-hydroxyethyl>-1-(triphenylmethyl)imidazole (176721-03-2) → 1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2)

Conditions	Yield
With triethylsilane; trifluoroacetic acid In dichloromethane at -10℃; for 4h;

trimethylsilyl-2,3-dimethylphenylacetylene → 1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: caesium carbonate / ethanol / 30 °C / Inert atmosphere 2.1: hydrogen bromide; acetic acid / dichloromethane / 0 - 10 °C / Inert atmosphere 3.1: sodium phosphate; tris-(dibenzylideneacetone)dipalladium(0) / 5,5-dimethyl-1,3-cyclohexadiene; water / 105 °C / Inert atmosphere 3.2: 1.5 h / 20 - 65 °C View Scheme

1-ethynyl-2,3-dimethylbenzene (767-87-3) → 1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: hydrogen bromide; acetic acid / dichloromethane / 0 - 10 °C / Inert atmosphere 2.1: sodium phosphate; tris-(dibenzylideneacetone)dipalladium(0) / 5,5-dimethyl-1,3-cyclohexadiene; water / 105 °C / Inert atmosphere 2.2: 1.5 h / 20 - 65 °C View Scheme

4-(2,3-dimethylbenzoyl)-1H-imidazole → 1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: tetrahydrofuran / 2 h / 0.4 - 65 °C / Large scale 2: toluene-4-sulfonic acid / toluene / 2 h / 0.11 °C / Dean-Stark View Scheme

1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2) + trityl chloride (76-83-5) → 4-(1-(2,3-dimethylphenyl)vinyl)-1-trityl-1H-imidazole

Conditions	Yield
With triethylamine In chloroform at 20 - 26℃; for 2h; Inert atmosphere;	100%

1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2) + benzyl chloroformate (501-53-1) → benzyl 4-(1-(2,3-dimethylphenyl)vinyl)-1H-imidazole-1-carboxylate

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 25h; Inert atmosphere;	99.2%

1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2) + p-toluenesulfonyl chloride (98-59-9) → 4-(1-(2,3-dimethylphenyl)vinyl)-1-tosyl-1H-imidazole

Conditions	Yield
With dmap; triethylamine In 1,2-dichloro-ethane at 20℃; for 2h; Inert atmosphere;	97.6%

1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2) + di-tert-butyl dicarbonate (24424-99-5) → tert-butyl 4-(1-(2,3-dimethylphenyl)vinyl)-1H-imidazole-1-carboxylate

Conditions	Yield
With triethylamine In tetrahydrofuran at 20℃; for 19h; Inert atmosphere;	96.9%

1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2) → 4-[(1S)-1-(2,3-dimethylphenyl)ethyl]-1H-imidazole hydrochloride

Conditions	Yield
With (1R,1’R,2S,2’S)-2,2’-di-tert-butyl-2,3,2’,3’-tetrahydro-1H,1‘H-(1,1‘)biisophosphindolyl; hydrogenchloride; bis(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate; hydrogen In toluene at 20℃; under 5171.62 Torr; for 10h; Solvent; Pressure;	91.6%

1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2) → (±)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole hydrochloride (86347-15-1)

Conditions	Yield
Stage #1: 1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene With hydrogen; 5%-palladium/activated carbon In methanol; water at 44 - 46℃; under 1575.16 Torr; for 1.5h; Stage #2: With hydrogenchloride In water at -10 - 42℃; for 2.5 - 3h;	89%

1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2) + methanesulfonyl chloride (124-63-0) → 4-(1-(2,3-dimethylphenyl)vinyl)-1-(methanesulfonyl)-1H-imidazole

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; for 2h; Inert atmosphere;	87.7%

1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2) → medetomidine (86347-14-0)

Conditions	Yield
With palladium on activated charcoal; hydrogen In methanol at 40℃;	84.6%
With palladium 10% on activated carbon; hydrogen at 10 - 20℃; under 760.051 - 1520.1 Torr;	4.2 g

1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2) + benzyl bromide (100-39-0) → 1-benzyl-4-(1-(2,3-dimethylphenyl)vinyl)-1H-imidazole (1311376-20-1)

Conditions	Yield
Stage #1: 1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 2h; Inert atmosphere; Stage #2: benzyl bromide In N,N-dimethyl-formamide at 20℃; for 2.5h; Inert atmosphere;	76.1%

1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2) + L-Tartaric acid (87-69-4) → (S)-dexmedetomidine-L-(+)-tartrate (176721-04-3)

Conditions	Yield
Stage #1: 1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene With (+)-1,2-bis((2S,5S)-diethylphospholano)benzene(cyclooctadiene)rhodium(I)trifluoromethanesulfonate; hydrogen In ethanol at 40 - 50℃; under 2280.15 - 3040.2 Torr; for 10h; Stage #2: L-Tartaric acid In ethanol at 70 - 80℃; for 0.5h; Solvent; Temperature; Pressure;	76.1%

1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2) + dimethylamino sulfonyl chloride (13360-57-1) → 4-(1-(2,3-dimethylphenyl)vinyl)-N,N-dimethyl-1H-imidazole-1-sulfonamide

Conditions	Yield
With triethylamine In chloroform at 20℃; for 23h; Inert atmosphere;	67.2%

1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2) + chloromethyl methyl ether (107-30-2) → 4-(1-(2,3-dimethylphenyl)vinyl)-1-(methoxymethyl)-1H-imidazole

Conditions	Yield
Stage #1: 1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene With sodium hydride In N,N-dimethyl-formamide at 4 - 20℃; for 1h; Inert atmosphere; Stage #2: chloromethyl methyl ether In N,N-dimethyl-formamide at 20 - 28℃; for 1.13333h; Inert atmosphere;	63.6%

1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2) + acetyl chloride (75-36-5) → 1-(4-(1-(2,3-dimethylphenyl)vinyl)-1H-imidazol-1-yl)ethan-1-one

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; for 3h; Inert atmosphere;	63.1%

1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2) + (2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) → 4-(1-(2,3-dimethylphenyl)vinyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole

Conditions	Yield
Stage #1: 1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 1.5h; Inert atmosphere; Stage #2: (2-trimethylethylsilylethoxy)methyl chloride In N,N-dimethyl-d6-formamide at 20℃; for 1h; Inert atmosphere;	53.9%

1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2) + O,O'-dibenzoyl-L-tartaric acid (2743-38-6) → C13H16N2*C18H14O8

Conditions	Yield
Stage #1: 1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene With bis(norbornadiene)rhodium(l)tetrafluoroborate; (2R)-1-[(1R)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(diphenylphosphino)ferrocene; hydrogen In methanol at 50℃; under 7500.75 Torr; for 22h; Glovebox; Stage #2: O,O'-dibenzoyl-L-tartaric acid In methanol at 20 - 25℃; for 3.75h; Inert atmosphere;	47%

1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2) → (+/-)-4(5)-<1-(2,3-Dimethylphenyl)ethyl-1H-imidazole> (86347-14-0)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 2068.65 Torr; for 8h;	36 mg

1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2) + p-toluenesulfonyl chloride (98-59-9) → 4-(1-(2,3-dimethylphenyl)ethyl)-1-tosyl-1H-imidazole

Conditions	Yield
Multi-step reaction with 2 steps 1: dmap; triethylamine / 1,2-dichloro-ethane / 2 h / 20 °C / Inert atmosphere 2: bis(norbornadiene)rhodium(l)tetrafluoroborate; hydrogen; (2S)-1-[(1S)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(diphenylphosphino)ferrocene / dichloromethane / 20 h / 10 °C / 6000.6 Torr View Scheme

1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2) + di-tert-butyl dicarbonate (24424-99-5) → tert-butyl-4-(1-(2,3-dimethylphenyl)ethyl)-1H-imidazole-1-carboxylate

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine / tetrahydrofuran / 19 h / 20 °C / Inert atmosphere 2: bis(norbornadiene)rhodium(l)tetrafluoroborate; hydrogen; (2S)-1-[(1S)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(diphenylphosphino)ferrocene / dichloromethane / 18 h / 10 °C / 6000.6 Torr View Scheme

1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethylene (1021949-47-2) + benzyl chloroformate (501-53-1) → benzyl-4-(1-(2,3-dimethylphenyl)ethyl)-1H-imidazole-1-carboxylate

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 25 h / 20 °C / Inert atmosphere 2: bis(norbornadiene)rhodium(l)tetrafluoroborate; hydrogen; (2S)-1-[(1S)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(diphenylphosphino)ferrocene / dichloromethane / 18 h / 10 °C / 6000.6 Torr View Scheme

Upstream product

• 176721-02-1 4-<(2,3-dimethylphenyl)carbonyl>-1-(triphenylmethyl)imidazole 
• 176721-01-0 4-<(2,3-dimethylphenyl)hydroxymethyl>-1-(triphenylmethyl)imidazole 
• 576-23-8 2,3-dimethylbromobenzene 
• 1779-49-3 Methyltriphenylphosphonium bromide 
• 5779-93-1 2,3-dimethylbenzaldehyde 
• 1900755-49-8 (1-trityl-1H-imidazol-4-yl)boronic acid 
• 176721-03-2 4-<1-(2,3-dimethylphenyl)-1-hydroxyethyl>-1-(triphenylmethyl)imidazole 
• 767-87-3 1-ethynyl-2,3-dimethylbenzene 

Downstream Products

• 86347-15-1 (±)-4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole hydrochloride 
• 86347-14-0 (+/-)-4(5)-<1-(2,3-Dimethylphenyl)ethyl-1H-imidazole> 
• 86347-14-0 medetomidine 
• 176721-04-3 (S)-dexmedetomidine-L-(+)-tartrate 
• 113775-47-6 dexmedetomidine 
• 1311376-20-1 1-benzyl-4-(1-(2,3-dimethylphenyl)vinyl)-1H-imidazole 

Relevant articles and documents

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):.

Preparation method of dexmedetomidine hydrochloride and its intermediate

The invention discloses a preparation method of dexmedetomidine hydrochloride and its intermediate. A preparation method of dexmedetomidine L-tartrate comprises the steps of subjecting dexmedetomidineintermediate III and hydrogen to reduction reaction in an organic solvent in the presence of a chiral catalyst, and subjecting the reduced product and tartaric acid to neutralization reaction to obtain dexmedetomidine L-tartrate II, wherein the chiral catalyst is (+)-1,2-bis(2S-5S)-diethylphospholano-benzene(1,5-cyclooctadiene)rhodium trifluoromethanesulfonate. The preparation method herein has ashort step path, has no need for chiral splitting, and has high total molar yield; the product prepared herein has high purity, reaches the standard for bulk pharmaceutical chemicals and is suitablefor industrial production.

A novel and facile route for the synthesis of medetomidine as the α2-adrenoceptor agonist

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.].