4-Bromophenol → (2R)-1-(4-bromophenoxy)-4-(3-pyridyl)-2-butanol

HRID 1856687Notes

Reaction equation

HRID 1856687 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[H-].[Na+].C1(C)C=CC(S(O[CH2:21][C@H:22]([O:31][Si](C(C)(C)C)(C)C)[CH2:23][CH2:24][C:25]2[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=2)(=O)=O)=CC=1.F.C(=O)([O-])O.[Na+]>CN(C)C=O.C(#N)C.O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:21][C@H:22]([OH:31])[CH2:23][CH2:24][C:25]2[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=2)=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 78084-BromophenolHCID 14917Hydrofluoric AcidHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 54162583(2R)-2-(tert-butyldimethylsilyloxy)-4-(3-pyridyl)-1-butyl para-toluenesulfonate

Product 1

HCID 53756856(2R)-1-(4-bromophenoxy)-4-(3-pyridyl)-2-butanolYield 82.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

Solid 4-bromophenol (2.08 g) was added to a stirred suspension of sodium hydride (60%, 0.48 g) in dimethylformamide (30 ml) and the resulting solution stirred for 30 minutes. (2R)-2-(tert-butyldimethylsilyloxy)-4-(pyridin-3-yl)-1-butyl para-toluenesulfonate (4.35 g, Example 5d)) 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 (20 ml) and hydrofluoric acid (40% in water; 5 ml, CAUTION) 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. The residue obtained was purified by column chromatography over silica eluting with acetone:hexane (1:1) to give the sub-title compound as a solid (2.65 g).

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
  13. customThe residue obtained
  14. customwas purified by column chromatography over silica eluting with acetone:hexane (1:1)

Sources & evidence

ORD record
ord-3304b8bcac274adcb49fcdf51b6cc270
Source dataset
uspto-grants-2000_11
Patent number
US06143751

Reaction notes

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