Hydrogen Bromide → 1-(4-Bromo-2-fluorophenyl)piperazine

HRID 57558Notes

Reaction equation

HRID 57558 reaction equation
N[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10][CH2:9]2)=[C:4]([F:21])[CH:3]=1.N([O-])=O.[Na+].[OH-].[Na+].[BrH:28]>O>[Br:28][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[C:4]([F:21])[CH:3]=1

Participants

6

Reactant 4

HCID 260Hydrogen Bromide2×HCID 14798Sodium HydroxideHCID 16203630tert-Butyl 4-(4-amino-2-fluorophenyl)piperazine-1-carboxylateHCID 23668193Sodium Nitrite

Product 1

HCID 32513091-(4-Bromo-2-fluorophenyl)piperazine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl 4-(4-amino-2-fluorophenyl)piperazine-1-carboxylate (885 mg, 3 mmol) in 8 mL of aq HBr was added a solution of NaNO2 (228 mg, 3.3 mmol) in 2 mL of H2O at 0° C., then the mixture was stirred at 0° C. for 40 minutes. After that, the mixture was poured into a solution of CuBr (905 mg, 6.3 mmol) in 8 mL aq HBr at 0° C. The reaction was heated to 60° C. and stirred for 2 hours. After cooling, the mixture was based with 2M NaOH to pH=8-9 and extracted with EA, washed with H2O and brine, dried and concentrated to give black solid. MS (m/z): 261 (M+H)+

Workup

  1. temperatureThe reaction was heated to 60° C.
  2. stirringstirred for 2 hours
  3. temperatureAfter cooling
  4. extractionextracted with EA
  5. washwashed with H2O and brine
  6. customdried
  7. concentrationconcentrated
  8. customto give black solid

Sources & evidence

ORD record
ord-4440b4b8e8754b9f8a5b54902b1bd457
Source dataset
uspto-grants-2016_09
Patent number
US09434726B2

Reaction notes

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