Imidazole → HCID 58452906, compound

HRID 70570Notes

Reaction equation

HRID 70570 reaction equation
[C:1]([Si:5]([CH3:8])([CH3:7])Cl)([CH3:4])([CH3:3])[CH3:2].N1C=CN=C1.[Br:14][C:15]1[CH:25]=[CH:24][C:18]([O:19][CH2:20][CH2:21][CH2:22][OH:23])=[CH:17][CH:16]=1.[Cl-].[NH4+]>CN(C)C=O.O>[Br:14][C:15]1[CH:25]=[CH:24][C:18]([O:19][CH2:20][CH2:21][CH2:22][O:23][Si:5]([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:8])[CH3:7])=[CH:17][CH:16]=1

Participants

7

Reactant 4

HCID 795ImidazoleHCID 25517Ammonium ChlorideHCID 28928tert-Butyldimethylsilyl chlorideHCID 187610183-(4-Bromophenoxy)propan-1-ol

Product 1

HCID 58452906HCID 58452906, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

tert-Butyldimethylchlorosilane (8.7 g) and imidazole (3.9 g) were added to a solution of 3-(4-bromophenoxy)propan-1-ol in N,N-dimethylformamide (193 mL) under ice-cooling, and the mixture was stirred at room temperature for 40 minutes. The reaction solution was ice-cooled and water and a saturated ammonium chloride solution were added, followed by extraction with a mixture of hexane-ethyl acetate (1:1). The organic layer was dried over sodium sulfate and filtered. The solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:1). Pyrrolidine (4.82 mL) and triethylamine (8.86 mL) were added to a solution of the resulting crude product in tetrahydrofuran (145 mL) under ice-cooling, and the mixture was stirred at room temperature for 27 hours. The reaction solution was ice-cooled and a saturated ammonium chloride solution was added, followed by extraction with a mixture of hexane-chloroform (1:1). The organic layer was dried over sodium sulfate and filtered. The solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:1→80:1) to give the title compound (7.88 g, 79% (two steps)).

Workup

  1. temperaturecooling
  2. temperaturecooled
  3. extractionfollowed by extraction with a mixture of hexane-ethyl acetate (1:1)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. customThe solvent was then evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:1)
  8. additionPyrrolidine (4.82 mL) and triethylamine (8.86 mL) were added to a solution of the resulting crude product in tetrahydrofuran (145 mL) under ice-
  9. temperaturecooling
  10. stirringthe mixture was stirred at room temperature for 27 hours
  11. temperaturecooled
  12. additiona saturated ammonium chloride solution was added
  13. extractionfollowed by extraction with a mixture of hexane-chloroform (1:1)
  14. dry with materialThe organic layer was dried over sodium sulfate
  15. filtrationfiltered
  16. customThe solvent was then evaporated under reduced pressure
  17. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:1→80:1)

Sources & evidence

ORD record
ord-c72be7e17ea0492797815131274a037e
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Reaction notes

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