Pyrrole → HCID 9904454, compound

HRID 1108552Notes

Reaction equation

HRID 1108552 reaction equation
[NH:1]1[CH:5]=[CH:4][CH: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>[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][CH:3]=[CH:2]1

Participants

5

Reactant 3

HCID 8027PyrroleHCID 24758Sodium hydrideHCID 15462731HCID 15462731, compound

Product 1

HCID 9904454HCID 9904454, compoundYield 58%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Pyrrole (0.299 ml) is dissolved in 7 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 2 hours at 50-60° C. The reaction is cooled, the dimethylformamide is removed under a stream of nitrogen, and the residue is washed with water followed by diethyl ether and is dried to give an off-white solid. The crude material is chromatographed over 25 g silica gel (230-400 mesh), eluting with 5% methanol/dichloromethane while collecting 5 ml fractions. Fractions 13-30 are combined and concentrated to give 520 mg (58%) of the title compound as a white solid, mp 176-177° C., [α]25D -73° (c 0.75).

Workup

  1. stirringthe reaction is stirred 2 hours at 50-60° C
  2. temperatureThe reaction is cooled
  3. customthe dimethylformamide is removed under a stream of nitrogen
  4. washthe residue is washed with water
  5. customis dried
  6. customto give an off-white solid
  7. customThe crude material is chromatographed over 25 g silica gel (230-400 mesh)
  8. washeluting with 5% methanol/dichloromethane
  9. customwhile collecting 5 ml fractions
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-9cc4ee2c579246eb9dd966af506918e8
Source dataset
uspto-grants-2000_05
Patent number
US06069141

Reaction notes

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