Trifluoroacetic acid → (4-Aminophenyl)(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)piperazin-1-yl)methanone

HRID 1807713Notes

Reaction equation

HRID 1807713 reaction equation
[NH2:1][C:2]1[CH:22]=[CH:21][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([C:14](OC(C)(C)C)=O)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.BrC[C:32]1[CH:37]=[CH:36][C:35]([C:38]([OH:47])([C:43]([F:46])([F:45])[F:44])[C:39]([F:42])([F:41])[F:40])=[CH:34][CH:33]=1.C(=O)([O-])[O-].[K+].[K+]>ClCCl.C(#N)C>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:9][CH2:10][N:11]([CH2:14][C:32]3[CH:37]=[CH:36][C:35]([C:38]([OH:47])([C:43]([F:44])([F:46])[F:45])[C:39]([F:42])([F:40])[F:41])=[CH:34][CH:33]=3)[CH2:12][CH2:13]2)=[O:7])=[CH:21][CH:22]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 2763355Tert-butyl 4-(4-aminobenzoyl)piperazine-1-carboxylateHCID 235273962-[4-(Bromomethyl)phenyl]-1,1,1,3,3,3-hexafluoropropan-2-ol

Product 1

HCID 86638547(4-Aminophenyl)(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)piperazin-1-yl)methanoneYield 54.4%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

tert-Butyl 4-(4-aminobenzoyl)piperazine-1-carboxylate (4.98 mmol, 1.520 g) was dissolved in dichloromethane and trifluoroacetic acid added. The reaction was left overnight and then treated to SCX purification. The intermediate amine was combined with 2-(4-(bromomethyl)phenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol (4.98 mmol, 1.678 g) and potassium carbonate (4.98 mmol, 0.688 g) in acetonitrile (30 mL) and stirred overnight. The reaction was concentrated under reduced pressure and the residue partitioned between water and ethyl acetate. The organic layer was separated and concentrated under reduced pressure. Purification by SCX column chromatography and silica chromatography (eluting with ethyl acetate) gave the title compound (1.25 g).

Workup

  1. additiontreated to SCX purification
  2. concentrationThe reaction was concentrated under reduced pressure
  3. customthe residue partitioned between water and ethyl acetate
  4. customThe organic layer was separated
  5. concentrationconcentrated under reduced pressure
  6. customPurification
  7. washby SCX column chromatography and silica chromatography (eluting with ethyl acetate)

Sources & evidence

ORD record
ord-f6ddc34564ef4f779d2af23656d5d23d
Source dataset
uspto-grants-2013_01
Patent number
US08357679B2

Reaction notes

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