Toluene → HCID 86670429, compound

HRID 1972675Notes

Reaction equation

HRID 1972675 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH2:9][CH:10]2[NH:15][CH2:14][CH2:13][N:12]([S:16]([C:19]3[S:20][CH:21]=[CH:22][CH:23]=3)(=[O:18])=[O:17])[CH2:11]2)[CH:6]=[CH:5][N:4]=1.Br[C:25]1[CH:30]=[CH:29][C:28]([C:31]([OH:40])([C:36]([F:39])([F:38])[F:37])[C:32]([F:35])([F:34])[F:33])=[CH:27][CH:26]=1.CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1>[NH4+].[Cl-].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:33][C:32]([F:34])([F:35])[C:31]([C:28]1[CH:27]=[CH:26][C:25]([N:15]2[CH2:14][CH2:13][N:12]([S:16]([C:19]3[S:20][CH:21]=[CH:22][CH:23]=3)(=[O:18])=[O:17])[CH2:11][CH:10]2[CH2:9][C:7]2[CH:6]=[CH:5][N:4]=[C:3]([O:2][CH3:1])[CH:8]=2)=[CH:30][CH:29]=1)([OH:40])[C:36]([F:37])([F:39])[F:38]

Participants

7

Reactant 4

HCID 1140TolueneHCID 232335702-(4-Bromophenyl)-1,1,1,3,3,3-hexafluoropropan-2-olHCID 23676156Sodium t-butoxideHCID 66583300HCID 66583300, compound

Product 1

HCID 86670429HCID 86670429, compoundYield 43.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
100 °C

Procedure

To a 50-mL round-bottomed flask was added 3-((2-methoxy-4-pyridinyl)methyl)-1-(2-thiophenylsulfonyl)piperazine (168 mg, 0.47 mmol), 2-(4-bromophenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol (184 mg, 0.57 mmol, Bioorg. Med. Chem. Lett. 2002, 12, 3009), dicyclohexyl(2′,4′,6′-triisopropyl-[1′,1′-biphenyl]-2-yl)phosphine (91 mg, 0.19 mmol, Strem, Newburyport, Mass.), tris(dibenzylideneacetone)dipalladium (43 mg, 0.05 mmol, Strem, Newburyport, Mass.), sodium tert-butoxide (137 mg, 1.43 mmol, Aldrich, St. Louis, Mo.), and toluene (5 mL). The reaction mixture was stirred at 100° C. for 18 h and allowed to cool to room temperature. The reaction mixture was diluted with saturated NH4Cl (20 mL) and extracted with EtOAc (2×30 mL). The organic extract was washed with saturated NaCl (5 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as a yellow oil. The crude product was purified by silica gel chromatography, eluting with 40% EtOAc/hexanes to give 1,1,1,3,3,3-hexafluoro-2-(4-(2-((2-methoxy-4-pyridinyl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol (121 mg) as a colorless oil.

Workup

  1. temperatureto cool to room temperature
  2. extractionextracted with EtOAc (2×30 mL)
  3. extractionThe organic extract
  4. washwas washed with saturated NaCl (5 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationThe solution was filtered
  7. concentrationconcentrated in vacuo
  8. customto give the crude material as a yellow oil
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with 40% EtOAc/hexanes

Sources & evidence

ORD record
ord-2a5f33c704c34a9aa00888ed7e751de5
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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