Acetic Acid → 2-[4-(2-ethyl-5-methyl-4-phenyl-1H-imidazol-1-yl)phenyl]ethanol

HRID 967821Notes

Reaction equation

HRID 967821 reaction equation
[OH:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH:11]([CH3:20])[C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=O)=[CH:6][CH:5]=1.[C:21](Cl)(=O)[CH2:22][CH3:23].C([O-])(=O)C.[NH4+:30].CC(O)=O>ClCCl.CO.[OH-].[Na+]>[CH2:22]([C:21]1[N:10]([C:7]2[CH:8]=[CH:9][C:4]([CH2:3][CH2:2][OH:1])=[CH:5][CH:6]=2)[C:11]([CH3:20])=[C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:30]=1)[CH3:23]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 62324Propionyl chlorideHCID 517165Ammonium AcetateHCID 222913492-{[4-(2-Hydroxyethyl)phenyl]amino}-1-phenyl-1-propanone

Product 1

HCID 222913982-[4-(2-ethyl-5-methyl-4-phenyl-1H-imidazol-1-yl)phenyl]ethanolYield 23.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 2-{[4-(2-hydroxyethyl)phenyl]amino}-1-phenyl-1-propanone (step 1 in EXAMPLE 3, 1.2 g, 4.5 mmol) in dichloromethane (10 mL) was added propionyl chloride (1.0 mL, 11.1 mmol) at ambient temperature. After 1 h, the reaction mixture was partitioned between ethyl acetate (30 mL) and water (10 mL). The aqueous phase was extracted with ethyl acetate (3×30 mL) and the combined organic phase was dried (MgSO4) and concentrated under reduced pressure. To the residue was added ammonium acetate (7.7 g, 100 mmol) and AcOH (15 mL) and the mixture was heated at 100° C. for 10 h. After cooling, the mixture was diluted with MeOH and basified with 4N NaOH aq. at 0° C. After 30 min, volatile components were removed under reduced pressure. The aqueous phase was extracted with dichloromethane (4×20 mL) and the combined organic phase was dried (MgSO4) and concentrated under reduced pressure. Purification by flash column chromatography on silica gel eluting with hexane/ethyl acetate (gradient elution from 1:1 to 1:2) to afford 0.32 g (23%) of the title compound as brown amorphous: 1H-NMR (CDCl3)δ1.19 (3H, t, J=7.5 Hz), 2.16 (3H, s), 2.57 (3H, q, J=7.5 Hz), 2.97 (2H, t, J=6.4 Hz), 3.96 (2H, t, J=6.4 Hz), 7.19-7.26 (3H, m), 7.38-7.43 (4H, m), 7.79 (2H, dd, J=7.1, 1.4 Hz).

Workup

  1. customthe reaction mixture was partitioned between ethyl acetate (30 mL) and water (10 mL)
  2. extractionThe aqueous phase was extracted with ethyl acetate (3×30 mL)
  3. dry with materialthe combined organic phase was dried (MgSO4)
  4. concentrationconcentrated under reduced pressure
  5. temperatureAfter cooling
  6. waitAfter 30 min
  7. customvolatile components were removed under reduced pressure
  8. extractionThe aqueous phase was extracted with dichloromethane (4×20 mL)
  9. dry with materialthe combined organic phase was dried (MgSO4)
  10. concentrationconcentrated under reduced pressure
  11. customPurification by flash column chromatography on silica gel eluting with hexane/ethyl acetate (gradient elution from 1:1 to 1:2)

Sources & evidence

ORD record
ord-9392528715a34da0ad15379c42c8a60e
Source dataset
uspto-grants-2005_10
Patent number
US06956050B2

Reaction notes

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