2-Chloro-N,N-dimethylethylamine → 2-(2-Dimethylaminoethylthio)-1-(3,5-difluorobenzyl)imidazole dihydrochloride

HRID 1639031Notes

Reaction equation

HRID 1639031 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:12]=[C:13]([F:15])[CH:14]=1)[CH2:5][N:6]1[CH:10]=[CH:9][N:8]=[C:7]1[SH:11].[OH-].[K+].[CH3:18][N:19]([CH3:23])[CH2:20][CH2:21][Cl:22].Cl.CN(CC[Cl:30])C.[OH-].[Na+]>CN(C)C=O.C1(C)C=CC=CC=1.O>[ClH:22].[ClH:30].[CH3:18][N:19]([CH3:23])[CH2:20][CH2:21][S:11][C:7]1[N:6]([CH2:5][C:4]2[CH:3]=[C:2]([F:1])[CH:14]=[C:13]([F:15])[CH:12]=2)[CH:10]=[CH:9][N:8]=1

Participants

10

Reactant 5

HCID 79012-Chloro-N,N-dimethylethylamineHCID 14797Potassium HydroxideHCID 14798Sodium HydroxideHCID 11636816N,N-Dimethylaminoethyl chloride hydrochlorideHCID 178505924HCID 178505924, compound

Product 1

HCID 198613862-(2-Dimethylaminoethylthio)-1-(3,5-difluorobenzyl)imidazole dihydrochloride

Reagents, catalysts & solvents 4

HCID 962WaterCatalystHCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 6228DimethylformamideSolvent

Procedure

1-(3,5-Difluorobenzyl)-2-mercaptoimidazole (2.26 g, 0.010) and potassium hydroxide (0.056 g, 0.01 mole) are dissolved in dimethylformamide (10 ml) containing water (0.5 ml) with stirring under argon at ambient temperature. To this solution is added dropwise 2-dimethylaminoethyl chloride (1.08 g, 0.010 mole) in toluene (10 ml). [This solution is prepared by stirring 1.44 g of dimethylaminoethyl chloride hydrochloride with an excess of sodium hydroxide pellets in the presence of toluene (10 ml) and a few drops of water, followed by filtering the solution of neutralized base.] The reaction mixture is warmed to 95° C., stirred at this temperature for one hour, cooled and then diluted with water. The layers are shaken together and separated and then the aqueous phase is extracted twice with ether. The toluene and ether extracts are combined and the solvents are removed in vacuo. The residual oil is dissolved in ether and hydrogen chloride in ether is added slowly with stirrinq until a slight excess is present. The precipitated white crystalline solid is filtered and recrystallized from ethanol ether to give 2-(2-dimethylaminoethylthio)-1-(3,5-difluorobenzyl)imidazole dihydrochloride.

Workup

  1. custom[This solution is prepared
  2. filtrationby filtering the solution of neutralized base
  3. temperature] The reaction mixture is warmed to 95° C.
  4. stirringstirred at this temperature for one hour
  5. temperaturecooled
  6. additiondiluted with water
  7. stirringThe layers are shaken together
  8. customseparated
  9. extractionthe aqueous phase is extracted twice with ether
  10. customthe solvents are removed in vacuo
  11. dissolutionThe residual oil is dissolved in ether
  12. additionhydrogen chloride in ether is added slowly with stirrinq until a slight
  13. filtrationThe precipitated white crystalline solid is filtered
  14. customrecrystallized from ethanol ether

Sources & evidence

ORD record
ord-0a1b468a92bb4cb5955db8ef9a77ef04
Source dataset
uspto-grants-1989_11
Patent number
US04882348

Reaction notes

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