Bromoacetonitrile → 1,1-Dimethylethyl 4-(cyanomethyl)-3-oxo-1-piperazinecarboxylate

HRID 1432934Notes

Reaction equation

HRID 1432934 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][C:10](=[O:14])[CH2:9]1)=[O:7])([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]([N:8]1[CH2:13][CH2:12][N:11]([CH2:18][C:19]#[N:20])[C:10](=[O:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 11534BromoacetonitrileHCID 24758Sodium hydrideHCID 3157178Tert-butyl 3-oxopiperazine-1-carboxylate

Product 1

HCID 543814791,1-Dimethylethyl 4-(cyanomethyl)-3-oxo-1-piperazinecarboxylateYield 54.3%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

4-(tert-Butyloxycarbonyl)-piperazin-2-one (8.0 g, 40 mmol), EXAMPLE 40, is dissolved in THF (160 mL), cooled in an ice bath and treated with 60% sodium hydride (1.9 g, 48 mmol). The reaction mixture is stirred 40 minutes, then treated with tetra-butylammonium iodide (0.35 g, 0.95 mmol) and bromoacetonitrile (3.4 mL, 48 mmol). After 2 h the reaction is quenched with water, concentrated to a small volume and extracted with methylene chloride (3×). The combined organic extracts are concentrated and the residue is chromatographed (50% ethyl acetate/hexane) to give 4-(tert-butyloxycarbonyl)-1-cyanomethyl-piperazin-2-one (5.2 g, 21.7 mmol). This material is dissolved in ethanol (140 mL) and treated with platinum oxide (0.83 g) at 50 PSI of hydrogen gas for 24 hours. The catalyst is removed by filtration and the solution is concentrated to yield 4-(tert-butyloxycarbonyl)-1-(2-aminoethyl)-piperazin-2-one (5.2 g, 21.6 mmol). 1H NMR (CDCl3, 300 MHz) δ4.08 (s, 2H), 3.62 (m, 2H), 3.44 (t, 2H), 3.38 (t, 2H), 2.89 (t, 2H).

Workup

  1. temperaturecooled in an ice bath
  2. customAfter 2 h the reaction is quenched with water
  3. concentrationconcentrated to a small volume
  4. extractionextracted with methylene chloride (3×)
  5. concentrationThe combined organic extracts are concentrated
  6. customthe residue is chromatographed (50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-2a43a79f9e0d4577889256923a55c517
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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