Imidazole → HCID 9926419, compound

HRID 1108553Notes

Reaction equation

HRID 1108553 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]=[CH:22][C:21](F)=[C:20]([F:25])[CH:19]=2)[CH2:14]1)(=[O:10])[CH3:9]>CN(C)C=O.C(OCC)(=O)C>[F:25][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]=[CH:22][C:21]=1[N:1]1[CH:5]=[CH:4][N:3]=[CH:2]1

Participants

6

Reactant 3

HCID 795ImidazoleHCID 24758Sodium hydrideHCID 15462731HCID 15462731, compound

Product 1

HCID 9926419HCID 9926419, compoundYield 28.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Imidazole (225 mg) is dissolved in 5 ml dimethylformamide in a 25 ml one neck round bottom flask under nitrogen. The solution is cooled to 0° C., is treated with 60% sodium hydride (132 mg), and the mixture is stirred 20 minutes at room temperature. The solution is treated with (-)-5-(acetamidomethyl)-3-(3,4-difluorophenyl)-isoxazoline (Step 1, Example 11) (763 mg), and the reaction is stirred 6 hours at 65° C. The reaction is cooled, is diluted with 25 ml ethyl acetate, and is washed with 4×25 ml 50% saturated 1:1 sodium chloride/sodium bicarbonate. The organics are dried over anhydrous magnesium sulfate and are concentrated in vacuo to a white solid. The crude material is chromatographed over 25 g silica gel (230-400 mesh), eluting with 4% methanol/dichloromethane while collecting 5 ml fractions. Fractions 33-69 are combined and concentrated to give 256 mg of a white solid which is washed with ethyl acetate to afford 227 mg (25%) of the title compound as a white solid, mp 155-156° C, [α]25D -76° (c 0.30).

Workup

  1. stirringthe reaction is stirred 6 hours at 65° C
  2. temperatureThe reaction is cooled
  3. washis washed with 4×25 ml 50% saturated 1:1 sodium chloride/sodium bicarbonate
  4. dry with materialThe organics are dried over anhydrous magnesium sulfate
  5. concentrationare concentrated in vacuo to a white solid
  6. customThe crude material is chromatographed over 25 g silica gel (230-400 mesh)
  7. washeluting with 4% methanol/dichloromethane
  8. customwhile collecting 5 ml fractions
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-d8a636cdc7354d6db97db838ca24099f
Source dataset
uspto-grants-2000_05
Patent number
US06069141

Reaction notes

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