tert-Butyl piperazine-1-carboxylate → 4-(3-Fluoro-4-trifluoromethyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1820776Notes

Reaction equation

HRID 1820776 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[C:4]([F:12])[CH:3]=1.[CH3:13][C:14]([O:17][C:18]([N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1)=[O:19])([CH3:16])[CH3:15].CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C>C1(C)C=CC=CC=1.CCOCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:14]([O:17][C:18]([N:20]1[CH2:25][CH2:24][N:23]([C:2]2[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[C:4]([F:12])[CH:3]=2)[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:13])[CH3:15]

Participants

8

Reactant 4

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 142277984-Chloro-2-fluoro-1-(trifluoromethyl)benzeneHCID 23676156Sodium t-butoxide

Product 1

HCID 597936284-(3-Fluoro-4-trifluoromethyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4.9 mmol 4-chloro-2-fluorobenzotrifluoride, 5.9 mmol n-Boc-piperazine, 0.05 mmol palladium acetate, 6.9 mmol sodium-t-butoxide and 0.49 mmol 2-(di-t-butylphosphino)biphenyl in 10 ml toluene was heated for 16 h at 80° C. After cooling to RT, the mixture was diluted with ether; the suspension was filtered over decalite; and the filtrate evaporated. The residue was purified on silica eluting with a gradient of heptane/EtOAc to yield after evaporation the title compound.

Workup

  1. temperatureAfter cooling to RT
  2. filtrationthe suspension was filtered over decalite
  3. customand the filtrate evaporated
  4. customThe residue was purified on silica eluting with a gradient of heptane/EtOAc
  5. customto yield
  6. customafter evaporation the title compound

Sources & evidence

ORD record
ord-d39c7fc2bd9d460e8e67f94de8043c00
Source dataset
uspto-grants-2009_10
Patent number
US07605163B2

Reaction notes

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