4-Hydroxybiphenyl → (2S)-4-(3-Pyridyl)-1-[(4-phenyl)phenoxy]-butan-2-ol

HRID 1600904Notes

Reaction equation

HRID 1600904 reaction equation
[C:1]1([C:7]2[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].C1(C)C=CC(S(O[CH2:26][C@@H:27]([O:36][Si](C(C)(C)C)(C)C)[CH2:28][CH2:29][C:30]2[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=2)(=O)=O)=CC=1.F.C(=O)([O-])O.[Na+]>CN(C)C=O.C(#N)C.O>[N:32]1[CH:33]=[CH:34][CH:35]=[C:30]([CH2:29][CH2:28][C@H:27]([OH:36])[CH2:26][O:13][C:10]2[CH:9]=[CH:8][C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[CH:12][CH:11]=2)[CH:31]=1

Participants

9

Reactant 5

HCID 71034-HydroxybiphenylHCID 14917Hydrofluoric AcidHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 57045765(2S)-2-(tert-Butyldimethylsilyloxy)-4-(3-pyridyl)-1-butyl para-toluenesulfonate

Product 1

HCID 57091781(2S)-4-(3-Pyridyl)-1-[(4-phenyl)phenoxy]-butan-2-olYield 70.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

Solid 4-phenylphenol (0.43 g) was added to a stirred suspension of sodium hydride (60%, 0.096 g) in dimethylformamide (5 ml) and the resulting solution stirred for 30 minutes. (2S)-2-(tert-Butyldimethylsilyloxy)-4-(3-pyridyl)-1-butyl para-toluenesulfonate (0.84 g) was added and the mixture stirred at 60° C. for 2 hours. After cooling the mixture was poured into water (50 ml) and extracted with ethyl acetate. The combined organic extracts were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue obtained was dissolved in acetonitrile (10 ml) and hydrofluoric acid (40%; 1 ml) was added. The mixture was stirred for 1 hour and then poured into a solution of saturated aqueous sodium hydrogencarbonate. The mixture was extracted with ethyl acetate and the combined organic extracts were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give the title compound (0.434 g) as a solid that was recrystallised from ethyl acetate:hexane.

Workup

  1. stirringthe mixture stirred at 60° C. for 2 hours
  2. temperatureAfter cooling the mixture
  3. extractionextracted with ethyl acetate
  4. dry with materialThe combined organic extracts were dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue obtained
  8. stirringThe mixture was stirred for 1 hour
  9. extractionThe mixture was extracted with ethyl acetate
  10. dry with materialthe combined organic extracts were dried over anhydrous magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b6366b00aed540378edb6c0ed1db6fe7
Source dataset
uspto-grants-1999_11
Patent number
US05977105

Reaction notes

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