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

HRID 1604424Notes

Reaction equation

HRID 1604424 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 22456823HCID 22456823, compoundHCID 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 the 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. customthe resulting reaction mixture
  4. stirringwas stirred for 16 hours at RT
  5. customThe solvent was evaporated
  6. additionmethyl isobutyl ketone (100 ml) was added
  7. customazeotroped on the rotary evaporator
  8. customThe mixture was purified by column chromatography over silica gel (eluent: CH2Cl2 /(CH3OH/NH3) 97/3)
  9. customThe desired fractions were collected
  10. customthe solvent was evaporated
  11. stirringThe white solid was stirred in diisopropyl ether
  12. filtrationfiltered off
  13. washwashed with DIPE
  14. customdried

Sources & evidence

ORD record
ord-99bcdae4a4e8401787bf7a9cfc7535b5
Source dataset
uspto-grants-1999_11
Patent number
US05994376

Reaction notes

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