tert-Butyl piperazine-1-carboxylate → Tert-butyl 4-(4-cyano-2-methylphenyl)piperazine-1-carboxylate

HRID 1726679Notes

Reaction equation

HRID 1726679 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[CH3:10].[N:11]1([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[C:20]([O:19][C:17]([N:11]1[CH2:16][CH2:15][N:14]([C:2]2[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=2[CH3:10])[CH2:13][CH2:12]1)=[O:18])([CH3:23])([CH3:21])[CH3:22]

Participants

5

Reactant 2

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 27374944-Bromo-3-methylbenzonitrile

Product 1

HCID 60051111Tert-butyl 4-(4-cyano-2-methylphenyl)piperazine-1-carboxylateYield 86.9%

Reagents, catalysts & solvents 2

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

Part 4: To a nitrogen flushed flask containing PdCl2dppf (65.8 mg, 0.081 mmol), dppf (44.6 mg, 0.081 mmol) and 4-bromo-3-methylbenzonitrile (631 mg, 3.22 mmol) in THF (5 mL) at −78° C. was added tert-butyl 1-piperazinecarboxylate (500 mg, 2.68 mmol) as a solid. The resultant mixture was heated to 100° C. and vigorously stirred overnight under nitrogen. The reaction was quenched with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried (MgSO4) and concentrated under reduced pressure. The residue was purified by flash chromatography (eluting with 0 to 30% ethyl acetate in hexane) to afford 4-(4-cyano-2-methyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (702 mg, 86.9%). MS (ESI): 302.0 (M+H+).

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography (eluting with 0 to 30% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-3cdf8ab9a7cb4c8ab210f9d665aa9822
Source dataset
uspto-grants-2009_02
Patent number
US07491724B2

Reaction notes

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