Sodium hydride → tert-Butyl N-[(3S)-1-(4-bromo-2-cyanophenyl)-5-oxopyrrolidin-3-yl]carbamate

HRID 715926Notes

Reaction equation

HRID 715926 reaction equation
[O:1]=[C:2]1[NH:6][CH2:5][C@@H:4]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:3]1.[H-].[Na+].[Br:17][C:18]1[CH:19]=[CH:20][C:21](F)=[C:22]([CH:25]=1)[C:23]#[N:24].[Cl-].[NH4+]>CN(C)C=O>[Br:17][C:18]1[CH:19]=[CH:20][C:21]([N:6]2[C:2](=[O:1])[CH2:3][C@H:4]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:11])([CH3:13])[CH3:12])[CH2:5]2)=[C:22]([C:23]#[N:24])[CH:25]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 27249005-Bromo-2-fluorobenzonitrileHCID 45091936(S)-tert-Butyl (5-oxopyrrolidin-3-yl)carbamate

Product 1

HCID 117893479tert-Butyl N-[(3S)-1-(4-bromo-2-cyanophenyl)-5-oxopyrrolidin-3-yl]carbamateYield 39.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of tert-butyl ((S)-5-oxopyrrolidin-3-yl)carbamate (2.0 g) in N,N-dimethylformamide (50 ml), sodium hydride (55% oil, 0.65 g) was added under ice cooling, and the mixture was stirred at the same temperature as above for 10 minutes. 5-Bromo-2-fluorobenzonitrile (3.0 g) was added to the reaction solution, and the mixture was stirred at room temperature for 1 hour. Ice water and a saturated aqueous solution of ammonium chloride were added to the reaction solution, followed by extraction with ethyl acetate. The extract was washed with water and saturated saline in this order and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane-ethyl acetate) to obtain the title compound (1.5 g).

Workup

  1. stirringthe mixture was stirred at room temperature for 1 hour
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe extract was washed with water and saturated saline in this order
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (n-hexane-ethyl acetate)

Sources & evidence

ORD record
ord-7117172d4ac4494abdf1dbb064138c19
Source dataset
uspto-grants-2015_11
Patent number
US09187489B2

Reaction notes

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