Methanol → Tert-butyl 4-(cyanomethyl)piperazine-1-carboxylate

HRID 1433069Notes

Reaction equation

HRID 1433069 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:17][C:18]#[N:19].CO>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:17][C:18]#[N:19])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 887MethanolHCID 11534BromoacetonitrileHCID 24758Sodium hydrideHCID 143452tert-Butyl piperazine-1-carboxylate

Product 1

HCID 21936030Tert-butyl 4-(cyanomethyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a partially dissolved solution of piperazine-1-carboxylic acid tert-butyl ester (2.0 g, 10 mmol) in THF (30 mL) is added 60% NaH (0.44 g, 11 mmol). The resulting solution is stirred for 5 min before the addition of bromoacetonitrile (0.9 mL, 13 mmol). The reaction is stirred for 4 h. MeOH (1 mL) is added and the solution is concentrated and the residue is diluted with EtOAc, washed with 1 N HCl, H2O, NaHCO3 and the solution is dried over MgSO4. The filtrate is concentrated and the crude product is chromatographed using a silica column (50% EtOAc/PE-EtOAc) to yield 4-cyanomethyl-piperazine-1-carboxylic acid tert-butyl ester. 1H NMR (300 MHz, CDCl3) δ4.41 (s, 2H), 4.16 (s, 2H), 3.75 (t, 2H), 3.51 (t, 2H), 1.47 (s, 9H).

Workup

  1. concentrationthe solution is concentrated
  2. additionthe residue is diluted with EtOAc
  3. washwashed with 1 N HCl, H2O, NaHCO3
  4. dry with materialthe solution is dried over MgSO4
  5. concentrationThe filtrate is concentrated
  6. customthe crude product is chromatographed

Sources & evidence

ORD record
ord-4e2d1bb1153f4260a8ade382b3e7a0f5
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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