Citric Acid → 1-(4-Fluorobenzoyl)-3-isopropyl-2-oxopyrrolidine-3-carbonitrile

HRID 714785Notes

Reaction equation

HRID 714785 reaction equation
[F:1][C:2]1[CH:17]=[CH:16][C:5]([C:6]([N:8]2[CH2:12][CH2:11][CH:10]([C:13]#[N:14])[C:9]2=[O:15])=[O:7])=[CH:4][CH:3]=1.[H-].[Na+].I[CH:21]([CH3:23])[CH3:22].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C)C=O>[F:1][C:2]1[CH:17]=[CH:16][C:5]([C:6]([N:8]2[CH2:12][CH2:11][C:10]([CH:21]([CH3:23])[CH3:22])([C:13]#[N:14])[C:9]2=[O:15])=[O:7])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 311Citric AcidHCID 6362Isopropyl iodideHCID 24758Sodium hydrideHCID 114361891-(4-Fluorobenzoyl)-2-oxo-3-pyrrolidinecarbonitrile

Product 1

HCID 1178410181-(4-Fluorobenzoyl)-3-isopropyl-2-oxopyrrolidine-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(4-fluorobenzoyl)-2-oxopyrrolidine-3-carbonitrile (500 mg) obtained in Step F of Example 1 in N,N-dimethylformamide (5 mL) was added sodium hydride (60% in mineral oil, 130 mg) in an ice bath, and the mixture was stirred at the same temperature for 5 min. To the reaction mixture was added 2-iodopropane (1.1 mL) in an ice bath, and the mixture was stirred at 50° C. for 1 hr. To the reaction mixture was added 10% aqueous citric acid solution in an ice bath, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (310 mg).

Workup

  1. stirringthe mixture was stirred at 50° C. for 1 hr
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-012d4172748e4d7f849cf8660f2e12c9
Source dataset
uspto-grants-2015_11
Patent number
US09187453B2

Reaction notes

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