Toluene → 3-Isopropyl-1-(2'-trifluoromethyl-biphenyl-4-ylmethyl)-piperazine

HRID 737146Notes

Reaction equation

HRID 737146 reaction equation
Br[C:2]1[CH:17]=[CH:16][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][NH:10][CH:9]([CH:13]([CH3:15])[CH3:14])[CH2:8]2)=[CH:4][CH:3]=1.[F:18][C:19]([F:30])([F:29])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>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(O)C>[CH:13]([CH:9]1[NH:10][CH2:11][CH2:12][N:7]([CH2:6][C:5]2[CH:16]=[CH:17][C:2]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[C:19]([F:30])([F:29])[F:18])=[CH:3][CH:4]=2)[CH2:8]1)([CH3:15])[CH3:14]

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27343872-(Trifluoromethyl)benzeneboronic acidHCID 578494561-(4-Bromo-benzyl)-3-isopropyl-piperazine

Product 1

HCID 578496493-Isopropyl-1-(2'-trifluoromethyl-biphenyl-4-ylmethyl)-piperazine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
120 °C

Procedure

100 mg of 1-(4-bromo-benzyl)-3-isopropyl-piperazine could be combined with 1 equiv. of 2-trifluoromethylphenyl boronic acid, 10 mol % of tetrakis(triphenylphosphine)palladium(0), 2M sodium carbonate solution, toluene and ethanol. The reaction mixture could be heated in a sealed tube at 120° C. overnight. The reaction mixture could be filtered through Celite and concentrated in vacuo. The residue could be diluted with water and extracted with ethyl acetate. The combined organic phases could be washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude material could be purified by flash chromatography to afford 3-isopropyl-1-(2′-trifluoromethyl-biphenyl-4-ylmethyl)-piperazine.

Workup

  1. filtrationThe reaction mixture could be filtered through Celite
  2. concentrationconcentrated in vacuo
  3. additionThe residue could be diluted with water
  4. extractionextracted with ethyl acetate
  5. washThe combined organic phases could be washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude material could be purified by flash chromatography

Sources & evidence

ORD record
ord-2ec8733508894c1092e57acf5f7a119e
Source dataset
uspto-grants-2009_09
Patent number
US07595397B2

Reaction notes

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