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

HRID 61417

Reaction equation

HRID 61417 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

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-0cc5f5dc19fe4cd4a5877ca158cdb183
Source dataset
uspto-grants-2016_09
Patent number
US09440958B2

Linked notes

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