Toluene → (S)-2-Benzyloxy-1-(3,5-bis(trifluoromethyl)phenyl)ethanol

HRID 990102Notes

Reaction equation

HRID 990102 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]1[CH:4]=[C:5]([C@H:13]([OH:16])[CH2:14][OH:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C([Sn](=O)CCCC)CCC.[C:29]1([CH3:35])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>>[CH2:35]([O:15][CH2:14][C@H:13]([C:5]1[CH:4]=[C:3]([C:2]([F:17])([F:18])[F:1])[CH:8]=[C:7]([C:9]([F:11])([F:12])[F:10])[CH:6]=1)[OH:16])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

4

Reactant 3

HCID 1140TolueneHCID 61221Dibutyltin oxideHCID 11161649(S)-1-(3,5-bis(Trifluoromethyl)phenyl)ethan-1,2-diol

Product 1

HCID 15497773(S)-2-Benzyloxy-1-(3,5-bis(trifluoromethyl)phenyl)ethanol

Procedure

(S)-1-(3,5-Bis(trifluoromethyl)phenyl)ethan-1,2-diol (11.45 g) and di-n-butyltin oxide (10.40 g) were dissolved in toluene (200 ml) and refluxed in a Dean and Stark apparatus for 16 hours. The toluene was removed under reduced pressure, cesium fluoride (12.70 g) suspended in N,N-dimethylformamide (200 ml) was added and the reaction stirred for 1 hour. The reaction was diluted with water and filtered through Hyflo™ before concentrating under reduced pressure and extracting into ethyl acetate. The organic phase was dried (brine, MgSO4) and concentrated under reduced pressure to give a crude brown oil. This was purified on silica eluting with 20% ethyl acetate/iso-hexane to afford the title compound as a pale yellow oil.

Workup

  1. temperaturerefluxed in a Dean and Stark apparatus for 16 hours
  2. customThe toluene was removed under reduced pressure, cesium fluoride (12.70 g)
  3. additionwas added
  4. additionThe reaction was diluted with water
  5. filtrationfiltered through Hyflo™
  6. concentrationbefore concentrating under reduced pressure
  7. extractionextracting into ethyl acetate
  8. dry with materialThe organic phase was dried (brine, MgSO4)
  9. concentrationconcentrated under reduced pressure
  10. customto give a crude brown oil
  11. customThis was purified on silica eluting with 20% ethyl acetate/iso-hexane

Sources & evidence

ORD record
ord-c4d7b245ade44bb8a5b1042c2f73b37f
Source dataset
uspto-grants-2002_10
Patent number
US06458830B1

Reaction notes

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