Cesium carbonate → 2-[4-(Trifluoromethoxy)phenoxy]ethanol

HRID 513184Notes

Reaction equation

HRID 513184 reaction equation
[F:1][C:2]([F:12])([F:11])[O:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.Br[CH2:14][CH2:15][O:16][Si](C(C)(C)C)(C)C.C([O-])([O-])=O.[Cs+].[Cs+].F.F.F.C(N(CC)CC)C>CN(C=O)C.CCCCCC.CCOC(C)=O>[F:1][C:2]([F:11])([F:12])[O:3][C:4]1[CH:5]=[CH:6][C:7]([O:10][CH2:14][CH2:15][OH:16])=[CH:8][CH:9]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 70015p-(Trifluoromethoxy)phenolHCID 175505N,N-Diethylethanamine trihydrofluorideHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilane

Product 1

HCID 211086172-[4-(Trifluoromethoxy)phenoxy]ethanolYield 87%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

4-trifluoromethoxyphenol (8.9 g, 50.2 mmol) was dissolved in DMF and treated with (2-bromoethoxy)(tert-butyl)dimethylsilane (16.81 g, 70.3 mmol) followed by Cs2CO3 (17.99 g, 55.2 mmol). The reaction mixture was heated to 60° C. for 3 hrs. The reaction was quenched with water and hexane was added. The two layers were separated, and the aqueous phase was further extracted twice with hexane. The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The resulting residue was used without further purification. The residue was dissolved in acetonitrile (100 mL) and treated with triethylamine trihydrofluoride (20.23 g, 125 mmol) the mixture was left to stir at RT for 3 hrs. TLC (10% EtOAc in hexane) showed the reaction was complete. Quenched with water (150 mL) and added ether (1000 mL). The organic layer was washed with brine, dried (Na2SO4) filtered and concentrated in vacuo. The residue was purified by silica gel chromatography. The eluting solvent was 0-20% EtOAc in hexanes. 9.7 g of the title product was isolated.

Workup

  1. customThe reaction was quenched with water and hexane
  2. additionwas added
  3. customThe two layers were separated
  4. extractionthe aqueous phase was further extracted twice with hexane
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe resulting residue was used without further purification
  10. dissolutionThe residue was dissolved in acetonitrile (100 mL)
  11. waitwas left
  12. customQuenched with water (150 mL)
  13. additionadded ether (1000 mL)
  14. washThe organic layer was washed with brine
  15. dry with materialdried (Na2SO4)
  16. filtrationfiltered
  17. concentrationconcentrated in vacuo
  18. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-e1abe45bb12941bba392226d3278dcf1
Source dataset
uspto-grants-2015_08
Patent number
US09102673B2

Reaction notes

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