Triethylamine → di-tert-butyl (2S)-2-(4-cyanophenyl)piperazine-1,4-dicarboxylate

HRID 1091381Notes

Reaction equation

HRID 1091381 reaction equation
[C:1](=[O:8])([O-])[O:2][C:3]([CH3:6])([CH3:5])[CH3:4].[C:9](=[O:16])([O-])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12].C(N(CC)CC)C.[C:24]([C:26]1[CH:31]=[CH:30][C:29]([C@H:32]2[CH2:37][NH:36][CH2:35][CH2:34][NH:33]2)=[CH:28][CH:27]=1)#[N:25]>O1CCCC1>[C:24]([C:26]1[CH:27]=[CH:28][C:29]([C@H:32]2[CH2:37][N:36]([C:9]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:16])[CH2:35][CH2:34][N:33]2[C:1]([O:2][C:3]([CH3:6])([CH3:5])[CH3:4])=[O:8])=[CH:30][CH:31]=1)#[N:25]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 1514410(2S)-2-(4-cyanophenyl)piperazineHCID 52911111Di-tert-butyl di-carbonate

Product 1

HCID 66594602di-tert-butyl (2S)-2-(4-cyanophenyl)piperazine-1,4-dicarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

1-Chloroethyl chloroformate (2.7 g, 18.9 mmol) was added to a solution of 4-((2S)-1,4-dibenzylpiperazin-2-yl)benzonitrile (1.4 g, 3.81 mmol) in dichloroethane (30 ml). The reaction mixture was vigorously stirred at room temperature for 10 hours. The solvent was evaporated under reduced pressure and methanol (40 ml) was added to the residue. The mixture was heated at 80° C. for one hour and the solvent was evaporated under reduced pressure to afford (2S)-2-(4-cyanophenyl)piperazine as white crystals. Di-tert-butyl di-carbonate (1.9 g, 8.71 mmol) was added to a solution of triethylamine (1.2 g, 11.9 mmol) and (2S)-2-(4-cyanophenyl)piperazine in tetrahydrofuran (50 ml) at room temperature and the mixture was stirred at 50° C. for one hour. The mixture was partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting 10-20% ethyl acetate in hexane to furnish di-tert-butyl

Workup

  1. customThe mixture was partitioned between water and ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel column chromatography
  6. washeluting 10-20% ethyl acetate in hexane
  7. customto furnish di-tert-butyl

Sources & evidence

ORD record
ord-f82839d170b64793a224eac83c979384
Source dataset
uspto-grants-2012_03
Patent number
US08129377B2

Reaction notes

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