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

HRID 619867Notes

Reaction equation

HRID 619867 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[O:21][C:20]([C:22]#[N:23])=[CH:19][CH:18]=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[O:21][C:20]([C:22]#[N:23])=[CH:19][CH:18]=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 108213955-(Bromomethyl)furan-2-carbonitrile

Product 1

HCID 54035945[1-(5-Cyanofuran-2-ylmethyl)-2-oxopyrrolidin-3-yl]carbamic acid tert-butyl esterYield 100%

Reagents, catalysts & solvents 1

HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

A solution of (2-oxopyrrolidin-3-(S)-yl)carbamic acid tert-butyl ester (1.56 g, 7.8 mmol) in 80 mL of THF:DMF (5:1) is treated with 5-bromomethylfuran-2-carbo-nitrile (3.23 g, 16 mmol) and sodium hydride (60%) (0.32 g, 8 mmol) as described in EXAMPLE 122, Part F. After addition, the solution is allowed to warm to ambient temperatures. After 5 hours, the solution is quenched by the addition of sat. NH4Cl. The solution is diluted with EtOAc and washed with H2O (3x) and saturated NaCl. The organic layer is dried over MgSO4, filtered and concentrated. The crude product is purified by column chromatography eluting with gradient of 40% EtOAc/hexanes to 80% EtOAc/hexanes to afford [1-(5-cyanofuran-2-ylmethyl)-2-oxopyrrolidin-3-yl]carbamic acid tert-butyl ester (2.38 g, 7.8 mmol) as a white solid. A portion of this material (1.28 g, 4.2 mmol) is treated as described in EXAMPLE 122, Part G to yield the title compound (1.1 g, 4.55 mmol).

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 EtOAc
  5. washwashed with H2O (3x) and saturated NaCl
  6. dry with materialThe organic layer is dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product is purified by column chromatography
  10. washeluting with gradient of 40% EtOAc/hexanes to 80% EtOAc/hexanes

Sources & evidence

ORD record
ord-23b6544e55c045a9a65d59d3cfe46abe
Source dataset
uspto-grants-1999_09
Patent number
US05958918

Reaction notes

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