Sodium hydride → HCID 9905524, compound

HRID 1108554Notes

Reaction equation

HRID 1108554 reaction equation
[CH:1]([C:3]1[CH:7]=[CH:6][NH:5][CH:4]=1)=[O:2].[H-].[Na+].[C:10]([NH:13][CH2:14][CH:15]1[O:19][N:18]=[C:17]([C:20]2[CH:25]=[CH:24][C:23](F)=[C:22]([F:27])[CH:21]=2)[CH2:16]1)(=[O:12])[CH3:11]>CN(C)C=O.C(OCC)(=O)C>[F:27][C:22]1[CH:21]=[C:20]([C:17]2[CH2:16][CH:15]([CH2:14][NH:13][C:10](=[O:12])[CH3:11])[O:19][N:18]=2)[CH:25]=[CH:24][C:23]=1[N:5]1[CH:6]=[CH:7][C:3]([CH:1]=[O:2])=[CH:4]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 6403081H-pyrrole-3-carboxaldehydeHCID 15462731HCID 15462731, compound

Product 1

HCID 9905524HCID 9905524, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

3-Formylpyrrole (628 mg) is dissolved in 12 ml dimethylformamide in a 50 ml one neck round bottom flask under nitrogen. The solution is cooled to 0° C., is treated with 60% sodium hydride (554 mg), and the mixture is stirred 30 minutes at room temperature. The solution is treated with (-)-5-(acetamidomethyl)-3-(3,4-difluorophenyl)-isoxazoline (Step 1, Example 11) (1.52 g), and the reaction is stirred 6 hours at 65° C. The reaction is cooled, is diluted with 100 ml ethyl acetate, and is washed with 4×25 ml 50% saturated sodium chloride. The organics are dried over anhydrous potassium carbonate and are concentrated in vacuo to a yellow oil. The crude material is chromatographed over 75 g silica gel (230-400 mesh) eluting with 3% methanol/dichloromethane and after a 200 ml forerun collecting 9 ml fractions. Fractions 48-69 are combined and concentrated to give 1.10 g (56%) of the title compound as a white solid, mp 155-156° C., [α]25D -69° (c 0.61, ethanol).

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 sodium chloride
  4. dry with materialThe organics are dried over anhydrous potassium carbonate
  5. concentrationare concentrated in vacuo to a yellow oil
  6. customThe crude material is chromatographed over 75 g silica gel (230-400 mesh)
  7. washeluting with 3% methanol/dichloromethane
  8. customafter a 200 ml forerun collecting 9 ml fractions
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-8240293aca374a04908d29f3cc7e7277
Source dataset
uspto-grants-2000_05
Patent number
US06069141

Reaction notes

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