Bromoacetonitrile → HCID 86584293, compound

HRID 651682Notes

Reaction equation

HRID 651682 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].[H-].[Na+].Br[CH2:18][C:19]#[N:20]>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:1]([O:5][C:6](=[O:14])[NH:7][C@H:8]1[CH2:12][CH2:11][N:10]([CH2:18][C:19]#[N:20])[C:9]1=[O:13])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 11534BromoacetonitrileHCID 24758Sodium hydrideHCID 10750535(S)-tert-Butyl (2-oxopyrrolidin-3-yl)carbamate

Product 1

HCID 86584293HCID 86584293, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

[2-Oxo-pyrrolidin-3(S)-yl]-carbamic acid tert-butyl ester (4.0 g, 20 mmol) is dissolved in THF (150 mL), cooled in an ice bath and treated with 60% sodium hydride (0.95 g, 24 mmol). The reaction mixture is stirred for 30 min., then treated with tetra-butylammonium iodide (0.16 g, 0.44 mmol) and bromoacetonitrile (1.7 mL, 24 mmol). After 3 h the reaction is quenched with water, concentrated to a small volume and extracted with methylene chloride (4×). The combined organic extracts are concentrated and the residue is chromatographed (2% MeOH/CH2Cl2) to give [1-cyanomethyl-2-oxo-pyrrolidin-3(S)-yl]-carbamic acid tert-butyl ester (3.4 g 14 mmol). ). EI MS m/z: 240, [M+1]+; 1H NMR (CDCl3, 300 MHz) δ5.08 (br, 1H), 4.27 (m, 2H), 4.15 (m, 1H), 3.47 (m, 2H), 2.68 (m, 1H), 2.00 (m, 1H), 1.45 (s, 9H). This material (3.0 g, 12.6 mmol) is dissolved in ethanol (80 mL) and treated with platinum oxide (0.8 g) at 50 PSI of hydrogen gas for 24 h. The catalyst is removed by filtration and the solution is concentrated to yield the title compound (2.9 g, 12 mmol). EI MS m/z: 244, [M+1]+; 1H NMR (CDCl3, 300 MHz) δ5.13 (br, 1H), 4.13 (m, 1H), 3.34 (m, 5H), 2.85 (t, 1H), 2.60 (m, 1H), 1.90 (m, 1H), 1.40 (s, 9H).

Workup

  1. temperaturecooled in an ice bath
  2. customAfter 3 h the reaction is quenched with water
  3. concentrationconcentrated to a small volume
  4. extractionextracted with methylene chloride (4×)
  5. concentrationThe combined organic extracts are concentrated
  6. customthe residue is chromatographed (2% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-37b7be1d36544f6b988989c2e5bcbd10
Source dataset
uspto-grants-2001_08
Patent number
US06281227B1

Reaction notes

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