2-Pyrrolidone → 1-(2-Fluoro-4-nitrophenyl)-2-pyrrolidinone

HRID 1971222Notes

Reaction equation

HRID 1971222 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][C:2]1=[O:6].[H-].[Na+].[F:9][C:10]1[CH:11]=[C:12]([N+:17]([O-:19])=[O:18])[CH:13]=[CH:14][C:15]=1F>CN(C=O)C>[F:9][C:10]1[CH:11]=[C:12]([N+:17]([O-:19])=[O:18])[CH:13]=[CH:14][C:15]=1[N:1]1[CH2:5][CH2:4][CH2:3][C:2]1=[O:6]

Participants

5

Reactant 3

HCID 120252-PyrrolidoneHCID 24758Sodium hydrideHCID 1230531,2-Difluoro-4-nitrobenzene

Product 1

HCID 534339651-(2-Fluoro-4-nitrophenyl)-2-pyrrolidinone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To 468 mg (5.5 mmol) of 2-pyrrolidone (Fluka, Buchs, Switzerland) in 10 ml of DMF at 0° C. are added 240 mg (5.5 mmol) of 55% NaH in oil. The reaction mixture is stirred for 30 min at 0° C. and for 30 min at rt. After this time, 795 mg (5 mmol) of 3,4-difluoronitrobenzene (Aldrich, Buchs, Switzerland) are added and the reaction mixture is stirred for 1 h at rt. The reaction mixture is quenched with 1 M aqueous HCl and extracted with EtOAc (2×). The organic layers are washed with aqueous sat. NaHCO3 and with brine (3×), dried over MgSO4, filtered and evaporated. The residue is purified by flash chromatography on silica gel (hexane-EtOAc 5:1 to 1:3) to give the title compound as a solid. ES-MS: 225 (M+H)+; analytical HPLC: tret=2.99 minutes (Grad 1).

Workup

  1. stirringthe reaction mixture is stirred for 1 h at rt
  2. customThe reaction mixture is quenched with 1 M aqueous HCl
  3. extractionextracted with EtOAc (2×)
  4. washThe organic layers are washed with aqueous sat. NaHCO3 and with brine (3×)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue is purified by flash chromatography on silica gel (hexane-EtOAc 5:1 to 1:3)

Sources & evidence

ORD record
ord-2b4c8bcfa8f24585bc4e47549708fa99
Source dataset
uspto-grants-2013_04
Patent number
US08431592B2

Reaction notes

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