2-Hydroxyimidazole → 1-[2-(3-Cyclopentyloxy-4-methoxy-phenyl)-2-oxo-ethyl]-1,3-dihydro-imidazol-2-one

HRID 2186512Notes

Reaction equation

HRID 2186512 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].N1C=CNC1=[O:16].COC1C=C(CC[N:29]2[CH2:33][CH2:32][N:31]([CH2:34][CH2:35][C:36]3[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[C:38]([O:44][CH3:45])[CH:37]=3)[C:30]2=[O:46])C=CC=1OC.[CH2:47]([C:51](C)=O)[CH:48](C)[CH3:49].O>CN(C=O)C>[CH:45]1([O:44][C:38]2[CH:37]=[C:36]([C:35](=[O:16])[CH2:34][N:31]3[CH:32]=[CH:33][NH:29][C:30]3=[O:46])[CH:41]=[CH:40][C:39]=2[O:42][CH3:43])[CH2:49][CH2:48][CH2:47][CH2:51]1

Participants

6

Reactant 4

HCID 222082-HydroxyimidazoleHCID 2724254Sodium bis(trimethylsilyl)amideHCID 224568231,3-bis[2-(3,4-dimethoxyphenyl)ethyl]-1,3,4,5-tetrahydro-2H-imidazol-2-oneHCID 22737866Isobutyl methyl ketone water

Product 1

HCID 99269351-[2-(3-Cyclopentyloxy-4-methoxy-phenyl)-2-oxo-ethyl]-1,3-dihydro-imidazol-2-oneYield 12.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium bis(trimethylsilyl)amide (5 ml) was added to a solution of 1,3-dihydro-2H-imidazol-2-one (0.84 g) in DMF (50 ml), stirred under a N2 flow and cooled in an ice-bath. The reaction mixture was stirred for 30 minutes. Intermediate 1 (2.69 g) was added portionwise and be resulting reaction mixture was stirred for 16 hours at RT, then for 2 hours at 50° C. The reaction mixture was stirred in methyl isobutyl ketone/water (200 ml/50 ml). The solvent was evaporated and methyl isobutyl ketone (100 ml) was added and azeotroped on the rotary evaporator. The mixture was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 97/3). The desired fractions were collected and the solvent was evaporated. The white solid was stirred in diisopropyl ether, filtered off, washed with DIPE and dried, yielding 0.4 g (12.6%) of 1-[2-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-oxo-ethyl]-1,3-dihydro-2H-imidazol-2-one (interm. 2; mp. 201.1° C).

Workup

  1. temperaturecooled in an ice-bath
  2. stirringThe reaction mixture was stirred for 30 minutes
  3. custombe resulting
  4. customreaction mixture
  5. stirringwas stirred for 16 hours at RT
  6. customThe solvent was evaporated
  7. additionmethyl isobutyl ketone (100 ml) was added
  8. customazeotroped on the rotary evaporator
  9. customThe mixture was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 97/3)
  10. customThe desired fractions were collected
  11. customthe solvent was evaporated
  12. stirringThe white solid was stirred in diisopropyl ether
  13. filtrationfiltered off
  14. washwashed with DIPE
  15. customdried

Sources & evidence

ORD record
ord-c09dfc2311814b629ecea749b09eb984
Source dataset
uspto-grants-2002_06
Patent number
US06403805B1

Reaction notes

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