4-Bromophenol → (1R,2R)-2-(4-bromophenoxy)cyclopentan-1-ol

HRID 2060832Notes

Reaction equation

HRID 2060832 reaction equation
[CH:1]12[O:6][CH:5]1[CH2:4][CH2:3][CH2:2]2.[Br:7][C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.O1CCOCC1>[Br:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C@@H:4]2[CH2:3][CH2:2][CH2:1][C@H:5]2[OH:6])=[CH:10][CH:9]=1

Participants

6

Reactant 3

HCID 78084-BromophenolHCID 92446-Oxabicyclo[3.1.0]hexane3×HCID 10796Cesium carbonate

Product 1

HCID 67195959(1R,2R)-2-(4-bromophenoxy)cyclopentan-1-ol

Reagents, catalysts & solvents 2

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 312751,4-DioxaneSolvent

Procedure

6-Oxabicyclo[3.1.0]hexane (2.04 mL, 23.5 mmol), 4-bromophenol (4.49 g, 26.0 mmol), cesium carbonate (99%, 8.93 g, 27.1 mmol) and benzyltriethylammonium chloride (99%, 1.09 g, 4.74 mmol) were suspended in dioxane (65 mL) and heated at reflux for 18 hours. Additional 6-oxabicyclo[3.1.0]hexane (0.50 mL, 5.8 mmol) was added, and heating was continued for 66 hours. Again, 6-oxabicyclo[3.1.0]hexane (0.50 mL, 5.8 mmol) was added, and the reaction mixture was heated at reflux for an additional 18 hours. The reaction was then cooled to room temperature, concentrated in vacuo and partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride solution, dried over calcium sulfate, filtered and concentrated under reduced pressure to afford a golden oil, which was purified via chromatography on silica gel (Gradient: 0% to 20% ethyl acetate in heptane) to provide product as an oil. Yield: 3.21 g, 12.5 mmol, 48%. GCMS m/z 256, 258 (M+). 1H NMR (400 MHz, CDCl3) δ 1.64 (d, J=3.7 Hz, 1H), 1.60-1.68 (m, 1H), 1.70-1.88 (m, 3H), 2.07 (m, 1H), 2.17 (m, 1H), 4.30 (m, 1H), 4.48 (m, 1H), 6.80 (d, J=9.0 Hz, 2H), 7.37 (d, J=9.0 Hz, 2H).

Workup

  1. temperatureheated
  2. temperatureat reflux for 18 hours
  3. temperatureheating
  4. temperaturethe reaction mixture was heated
  5. temperatureat reflux for an additional 18 hours
  6. concentrationconcentrated in vacuo
  7. custompartitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate
  8. washThe organic layer was washed with saturated aqueous sodium chloride solution
  9. dry with materialdried over calcium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customto afford a golden oil, which
  13. customwas purified via chromatography on silica gel (Gradient: 0% to 20% ethyl acetate in heptane)
  14. customto provide product as an oil

Sources & evidence

ORD record
ord-c21d68a3f3bd4462aefb7fda72284ff4
Source dataset
uspto-grants-2012_10
Patent number
US08278457B2

Reaction notes

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