Imidazole → HCID 9948972, compound

HRID 1108560Notes

Reaction equation

HRID 1108560 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[H-].[Na+].[C:8]([NH:11][CH2:12][CH:13]1[O:17][N:16]=[C:15]([C:18]2[CH:23]=[C:22]([F:24])[C:21](F)=[C:20]([F:26])[CH:19]=2)[CH2:14]1)(=[O:10])[CH3:9].CO>CN(C=O)C.O.C(Cl)Cl>[F:26][C:20]1[CH:19]=[C:18]([C:15]2[CH2:14][CH:13]([CH2:12][NH:11][C:8](=[O:10])[CH3:9])[O:17][N:16]=2)[CH:23]=[C:22]([F:24])[C:21]=1[N:1]1[CH:5]=[CH:4][N:3]=[CH:2]1

Participants

8

Reactant 4

HCID 795ImidazoleHCID 887MethanolHCID 24758Sodium hydrideHCID 18783756HCID 18783756, compound

Product 1

HCID 9948972HCID 9948972, compoundYield 56.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

A solution of imidazole (42 mg) in dry DMF (5 mL) is treated with 60% sodium hydride dispersion in mineral oil (25 mg), stirred for 3 minutes and treated with (-)-5-(acetamidomethyl)-3-(3,4,5-trifluorophenyl)isoxazoline (see Example 25) (150 mg). After 18 hours, the mixture is heated to 40° C. for 2 hours. TLC analysis (5% CH3OH--CH2Cl2) indicated the reaction to be virtually complete. The mixture is diluted with water (50 mL) and extracted with EtOAc (6×20 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give a white solid. Chromatography over silica (radial chromatography, 2 mm plate) eluting with CH2Cl2, 2% and 5% CH3OH--CH2Cl2 gives 100 mg of the title compound as a white solid, mp 168-169° C., [α]25D -80° (c 0.61, DMSO).

Workup

  1. waitAfter 18 hours
  2. customthe reaction
  3. extractionextracted with EtOAc (6×20 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give a white solid
  8. washChromatography over silica (radial chromatography, 2 mm plate) eluting with CH2Cl2, 2% and 5% CH3OH

Sources & evidence

ORD record
ord-6e94bf755d644f09b200b8a7226153eb
Source dataset
uspto-grants-2000_05
Patent number
US06069141

Reaction notes

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