4-Bromophenol → trans-4-(4-Bromophenoxy)tetrahydrofuran-3-ol

HRID 2360320Notes

Reaction equation

HRID 2360320 reaction equation
[CH:1]12[O:6][CH:5]1[CH2:4][O: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.C(OCC)(=O)C>[Br:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C@@H:5]2[CH2:4][O:3][CH2:2][C@H:1]2[OH:6])=[CH:10][CH:9]=1

Participants

7

Reactant 3

HCID 78084-BromophenolHCID 10796Cesium carbonateHCID 675113,6-Dioxabicyclo[3.1.0]hexane

Product 1

HCID 67195067trans-4-(4-Bromophenoxy)tetrahydrofuran-3-ol

Reagents, catalysts & solvents 3

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

3,6-Dioxabicyclo[3.1.0]hexane (100 g, 1.16 mol), 4-bromophenol (241.1 g, 1.39 mol), cesium carbonate (492 g, 1.51 mol) and benzyltriethylammonium chloride (52.9 g, 0.23 mol) were suspended in dioxane (1 L) and heated at reflux for 18 hours. The reaction was cooled to room temperature and diluted with ethyl acetate, then washed with saturated aqueous sodium carbonate solution. The aqueous layer was extracted with ethyl acetate, and the combined organic portions were dried over sodium sulfate, filtered and concentrated in vacuo, to provide crude product, which solidified on standing. This was used without purification in the next step. Yield: 354 g, >100%, assumed quantitative. Material from a smaller-scale experiment carried out in similar fashion was purified by silica gel chromatography for characterization (Gradient: 10% to 35% ethyl acetate in heptane), to afford trans-4-(4-bromophenoxy)tetrahydrofuran-3-ol as a solid. 1H NMR (400 MHz, CDCl3) δ 2.09 (br d, J=4.5 Hz, 1H), 3.83 (m, 1H), 3.91 (dd, J=10.3, 2.1 Hz, 1H), 4.05 (dd, J=10.1, 4.0 Hz, 1H), 4.26 (dd, J=10.4, 4.9 Hz, 1H), 4.41 (br s, 1H), 4.67 (m, 1H), 6.81 (d, J=9.0 Hz, 2H), 7.40 (d, J=9.1 Hz, 2H).

Workup

  1. temperatureheated
  2. temperatureat reflux for 18 hours
  3. washwashed with saturated aqueous sodium carbonate solution
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. dry with materialthe combined organic portions were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto provide crude product, which
  9. customThis was used without purification in the next step
  10. customwas purified by silica gel chromatography for characterization (Gradient: 10% to 35% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-94ba0d7c7b664041b35090319c3612da
Source dataset
uspto-grants-2014_04
Patent number
US08686043B2

Reaction notes

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