Water → (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(4-methoxybenzyl)piperazine

HRID 1375044Notes

Reaction equation

HRID 1375044 reaction equation
[F:1][C:2]([F:38])([F:37])[C:3]1[CH:4]=[C:5]([CH:30]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:32]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11](CC2C=CC=CC=2)[CH2:10][C@H:9]1[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=1)=[O:7].O.C([O-])=O.[NH4+]>C(O)C.[Pd]>[F:38][C:2]([F:1])([F:37])[C:3]1[CH:4]=[C:5]([CH:30]=[C:31]([C:33]([F:34])([F:35])[F:36])[CH:32]=1)[C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][C@H:9]1[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=1)=[O:7]

Participants

6

Reactant 3

HCID 962WaterHCID 2723923Ammonium formateHCID 53698566(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(4-methoxybenzyl)-4-benzylpiperazine

Product 1

HCID 54306763(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(4-methoxybenzyl)piperazineYield 78%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (2R)-1-[3,5-bis(trifluoromethyl)-benzoyl]-2-(4-methoxybenzyl)-4-benzylpiperazine (4.90 g) in ethanol (50 ml) were added water (5 ml), ammonium formate (1.44 g), and 10% palladium on activated carbon [50% wet] (0.49 g) under nitrogen atmosphere. The reaction mixture was heated at 60° C. with stirring for 2 hours. Insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. Ethyl acetate (40 ml) and water (40 ml) were added to the residue, and the organic layer was separated, washed with brine, and dried over magnesium sulfate. After removal of the solvent by evaporation, the resulting residue was purified by column chromatography on silica gel (70 g) using a mixed solvent of ethyl acetate and methanol (10:1). The fractions containing the objective compound were collected and evaporated under reduced pressure to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(4-methoxybenzyl)piperazine (3.18 g) as syrup.

Workup

  1. customInsoluble material was removed by filtration
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. additionEthyl acetate (40 ml) and water (40 ml) were added to the residue
  4. customthe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over magnesium sulfate
  7. customAfter removal of the solvent
  8. customby evaporation
  9. customthe resulting residue was purified by column chromatography on silica gel (70 g)
  10. additionThe fractions containing the objective compound
  11. customwere collected
  12. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-65878ed94aa041098f8e16bb042b7254
Source dataset
uspto-grants-2007_01
Patent number
US07166598B2

Reaction notes

Loading…