Chloroacetic Acid → 2-(Carboxymethylthio)-1-(3,5-difluorobenzyl)imidazole

HRID 2107636Notes

Reaction equation

HRID 2107636 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].Cl[CH2:17][C:18]([OH:20])=[O:19].[OH-].[K+].Cl>CN(C)C=O.O>[C:18]([CH2:17][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)([OH:20])=[O:19]

Participants

7

Reactant 4

HCID 300Chloroacetic AcidHCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 178505924HCID 178505924, compound

Product 1

HCID 151145952-(Carboxymethylthio)-1-(3,5-difluorobenzyl)imidazoleYield 42%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent3×HCID 6228DimethylformamideSolvent

Procedure

1-(3,5-Difluorobenzyl)-2-mercaptoimidazole (2.26 g, 0.010 mole) and chloroacetic acid (0.95 g, 0.010 mole) were dissolved in a mixture of dimethylformamide (10 ml) and water (0.5 ml), and potassium hydroxide (1.12 g, 0.020 mole) in water (10 ml) was added dropwise with stirring at ambient temperature over 30 minutes. Stirring at ambient temperature was continued for five hours. The solution was then diluted with water (10 ml) and acidified with concentrated hydrochloric acid. A trace of precipitate formed. The mixture was filtered and the pH of the filtrate was adjusted to 5.5 with concentrated ammonium hydroxide and the mixture was extracted with three portions of methylene chloride. Concentration of the combined extracts gave a clear, heavy oil which was triturated with boiling ether. A white crystalline solid formed which was filtered and recrystallized from ethyl acetate hexane to give 1.18 g (42% yield) of 2-(carboxymethylthio)-1-(3,5-difluorobenzyl)imidazole, mp 101°-103° C.

Workup

  1. additionwas added dropwise
  2. stirringStirring at ambient temperature
  3. waitwas continued for five hours
  4. customA trace of precipitate formed
  5. filtrationThe mixture was filtered
  6. extractionthe mixture was extracted with three portions of methylene chloride
  7. customConcentration of the combined extracts gave a clear, heavy oil which
  8. customwas triturated with boiling ether
  9. customA white crystalline solid formed which
  10. filtrationwas filtered
  11. customrecrystallized from ethyl acetate hexane

Sources & evidence

ORD record
ord-6c77deba5e074acc849903a760f8dcba
Source dataset
uspto-grants-1990_06
Patent number
US04935438

Reaction notes

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