p-Fluoronitrobenzene → (S)-1-(4-nitro-phenyl)-5-oxo-pyrrolidine-2-carboxylic acid tert-butyl ester

HRID 469728

Reaction equation

[C:1]([O:5][C:6]([C@@H:8]1[CH2:12][CH2:11][C:10](=[O:13])[NH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].F[C:17]1[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][CH:18]=1.[Cl-].[NH4+]>CS(C)=O>[C:1]([O:5][C:6]([C@@H:8]1[CH2:12][CH2:11][C:10](=[O:13])[N:9]1[C:17]1[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][CH:18]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 80 °C

Procedure

To a stirred solution of (S)-5-oxo-pyrrolidine-2-carboxylic acid tert-butyl ester (1.85 g, 10 mmol) in dimethylsulfoxide (10 mL) at room temperature, sodium hydride (440 mg of 60% dispersion in mineral oil, 11 mmol) is added in portions over a period of 20 min. After 30 min, 4-fluoronitrobenzene (1.06 mL, 10 mmol) is added and the mixture is heated by placing in an oil-bath maintained at 80° C. for 4 h. The reaction mixture is allowed to cool to room temperature, treated with saturated ammonium chloride solution (150 mL) and extracted with ethyl acetate (250 mL). Organic extracts are combined, washed with brine (100 mL), dried over anhydrous Na2SO4 and solvent removed in vacuo. The crude is purified chromatography over silica gel eluting with hexanes/ethyl acetate and the title compound is obtained as a light yellow solid, ESI m/z 307 [M+H]+.

Workup

temperaturethe mixture is heated
customby placing in an oil-bath
temperatureto cool to room temperature
extractionextracted with ethyl acetate (250 mL)
washwashed with brine (100 mL)
dry with materialdried over anhydrous Na2SO4 and solvent
customremoved in vacuo
customThe crude is purified chromatography over silica gel eluting with hexanes/ethyl acetate

Sources & evidence

ORD record: ord-222aa04b76424d3fbacd196df57fa757
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08629157B2

Linked notes

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