Dimethylformamide → Tert-butyl 4-(2-tert-butyl-4-cyanophenyl)piperazine-1-carboxylate

HRID 534964Notes

Reaction equation

HRID 534964 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[C:4]([C:21]([CH3:24])([CH3:23])[CH3:22])[CH:3]=1.C([O-])(O)=O.[Na+].[CH3:30][N:31](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:21]([C:4]1[CH:3]=[C:2]([C:30]#[N:31])[CH:7]=[CH:6][C:5]=1[N:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1)([CH3:24])([CH3:23])[CH3:22]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 66751044Tert-butyl 4-(4-bromo-2-tert-butylphenyl)piperazine-1-carboxylate

Product 1

HCID 66751177Tert-butyl 4-(2-tert-butyl-4-cyanophenyl)piperazine-1-carboxylateYield 88%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

A mixture of tert-butyl 4-(4-bromo-2-tert-butylphenyl)piperazine-1-carboxylate (Example 85, 3.0 g, 7.55 mmol), zinc cyanide (1.77 g, 15.1 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.88 g, 0.76 mmol) in DMF (30 mL) was stirred at 100° C. for 4 h under argon atmosphere. The reaction mixture was cooled to room temperature, poured into saturated NaHCO3 solution and extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4, and the solvent was evaporated under reduced pressure to give the crude product. The product was purified by flash column chromatography (silica gel, n-hexane/ethyl acetate=95:5 to 80:20) to provide tert-butyl 4-(2-tert-butyl-4-cyanophenyl)piperazine-1-carboxylate (2.29 g, 88%) as a white powder.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. customthe solvent was evaporated under reduced pressure
  6. customto give the crude product
  7. customThe product was purified by flash column chromatography (silica gel, n-hexane/ethyl acetate=95:5 to 80:20)

Sources & evidence

ORD record
ord-15de118c503e425b9e4e5ea0d3b01f5a
Source dataset
uspto-grants-2014_10
Patent number
US08853215B2

Reaction notes

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