1-Bromo-2-Chloroethane → tert-butyl 4-(2-(4-iodo-1H-imidazol-1-yl)ethyl)piperazine-1-carboxylate

HRID 1400916Notes

Reaction equation

HRID 1400916 reaction equation
[I:1][C:2]1[N:3]=[CH:4][NH:5][CH:6]=1.Br[CH2:8][CH2:9]Cl.C([O-])([O-])=O.[K+].[K+].[C:17]([N:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1)([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18]>CS(C)=O>[I:1][C:2]1[N:3]=[CH:4][N:5]([CH2:8][CH2:9][N:27]2[CH2:26][CH2:25][N:24]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:29][CH2:28]2)[CH:6]=1

Participants

6

Reactant 4

HCID 78491-Bromo-2-Chloroethane2×HCID 11430Potassium CarbonateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 178506559HCID 178506559, compound

Product 1

HCID 67442735tert-butyl 4-(2-(4-iodo-1H-imidazol-1-yl)ethyl)piperazine-1-carboxylateYield 8%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 4-iodoimidazole (25 g, 129 mmol) and 1-bromo-2-chloroethane (12.87 ml, 155 mmol) in DMSO (250 ml) under nitrogen was added K2CO3 (26.7 g, 193 mmol). The reaction mixture was heated at 80° C. for 30 min. More 1-bromo-2-chloroethane (1.28 ml, 15.5 mmol) was added and the reaction mixture was heated at 80° C. for an additional 30 min. Finally, 1-Boc-piperazine (28.8 g, 155 mmol) was added and the reaction mixture heated at 80° C. for 1 h, cooled to RT and partitioned between water and AcOEt. The organic layer was collected, washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by Biotage (SNAP 340 g cartridge; Hexane/AcOEt:40/60 to 0/100 over 15 CV) followed by another purification under different conditions (SNAP 100 g cartridge; MeOH/DCM: 0/100 to 5/95 over 15 CV), to afford title compound 304 (4 g, 9.85 mmol, 8% yield) as white solid. MS (m/z): 407.18 (M+H).

Workup

  1. temperaturethe reaction mixture was heated at 80° C. for an additional 30 min
  2. temperaturethe reaction mixture heated at 80° C. for 1 h
  3. temperaturecooled to RT
  4. custompartitioned between water and AcOEt
  5. customThe organic layer was collected
  6. washwashed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by Biotage (SNAP 340 g cartridge; Hexane/AcOEt:40/60 to 0/100 over 15 CV)
  11. customfollowed by another purification under different conditions (SNAP 100 g cartridge; MeOH/DCM: 0/100 to 5/95 over 15 CV)

Sources & evidence

ORD record
ord-e6498c91cad3416ba2ad250dd159c324
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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