Sodium hydride → [1-(5-Cyanothiophene-3-ylmethyl)-2-oxopyrrolidin-3-yl]carbamic acid tert-butyl ester

HRID 619836Notes

Reaction equation

HRID 619836 reaction equation
[C:1]([O:5][C:6](=[O:14])[NH:7][C@H:8]1[CH2:12][CH2:11][NH:10][C:9]1=[O:13])([CH3:4])([CH3:3])[CH3:2].Br[CH2:16][C:17]1[CH:18]=[C:19]([C:22]#[N:23])[S:20][CH:21]=1.[H-].[Na+]>C1COCC1.CN(C=O)C>[C:1]([O:5][C:6](=[O:14])[NH:7][CH:8]1[CH2:12][CH2:11][N:10]([CH2:16][C:17]2[CH:18]=[C:19]([C:22]#[N:23])[S:20][CH:21]=2)[C:9]1=[O:13])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 10750535(S)-tert-Butyl (2-oxopyrrolidin-3-yl)carbamateHCID 107506074-(Bromomethyl)thiophene-2-carbonitrile

Product 1

HCID 53990976[1-(5-Cyanothiophene-3-ylmethyl)-2-oxopyrrolidin-3-yl]carbamic acid tert-butyl esterYield 86.3%

Reagents, catalysts & solvents 1

HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

To a solution of (2-oxopyrrolidin-3-(S)-yl)carbamic acid tert-butyl ester (3.2 g, 16 mmol) in 80 mL of THF:DMF (10:1) at 0° C. is added 4-bromomethylthiophene-2-carbonitrile (3.23 g, 16 mmol) and sodium hydride (60%) (0.67 g, 16.8 mmol). After addition, the solution is allowed to warm to ambient temperatures. After 2 hours, the solution is quenched by the addition of sat NH4Cl. The solution is diluted with H2O and EtOAc. The layers are separated. The organic layer is washed with H2O and sat. NaCl. The organic layer is dried over MgSO4, filtered and concentrated. The crude product is purified by column chromatography eluting with gradient of 20% EtOAc/CH2Cl2 to 30% EtOAc/CH2Cl2 to afford the title compound (4 g, 13.8 mmol) as a white solid.

Workup

  1. additionAfter addition
  2. temperatureto warm to ambient temperatures
  3. customthe solution is quenched by the addition of sat NH4Cl
  4. additionThe solution is diluted with H2O and EtOAc
  5. customThe layers are separated
  6. washThe organic layer is washed with H2O and sat. NaCl
  7. dry with materialThe organic layer is dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product is purified by column chromatography
  11. washeluting with gradient of 20% EtOAc/CH2Cl2 to 30% EtOAc/CH2Cl2

Sources & evidence

ORD record
ord-122bc5dd32e04e7fa1892e792ab62b8d
Source dataset
uspto-grants-1999_09
Patent number
US05958918

Reaction notes

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