Sodium hydride → [1-(5-Cyanothiophen-3-ylmethyl)-2-oxo-pyrrolidin-3-(S)-yl]-carbamic acid tert-butyl ester

HRID 2750

Reaction equation

HRID 2750 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][C@H: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 10615767[1-(5-Cyanothiophen-3-ylmethyl)-2-oxo-pyrrolidin-3-(S)-yl]-carbamic acid tert-butyl esterYield 86.3%

Reagents, catalysts & solvents 1

HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

To a solution of (2-oxo-pyrrolidin-3-(S)-yl)-carbamic acid tert-butyl ester (3.2 g, 16 mmol), prepared as described in EXAMPLE 1, Part A in 80 mL of THF:DMF (10:1) at 0° C. is added 4-bromomethyl-thiophene-2-carbonitrile (3.23 g, 16 mmol) and sodium hydride (60% dispersion in oil, 0.67 g, 16.8 mmol). After addition, the solution was allowed to warm to ambient temperatures. After 2 h, 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/CH2 Cl2 to 30% EtOAc/CH2Cl2 to afford the title compound (4.0 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/CH2 Cl2 to 30% EtOAc/CH2Cl2

Sources & evidence

ORD record
ord-84a55dcc108c4ee98e6877dc7c417430
Source dataset
uspto-grants-1998_03
Patent number
US05731315

Linked notes

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