Phenol → Estra-4,9,16-trien-3-one

HRID 2270523Notes

Reaction equation

HRID 2270523 reaction equation
[CH3:1][C@:2]12[CH2:18][CH2:17][C@H:16]3[C@@H:7]([CH2:8][CH2:9][C:10]4[CH2:11][C:12](=[O:19])[CH2:13][CH2:14][C:15]=43)[C@@H:6]1[CH2:5][CH:4]=[CH:3]2.N1C=CC=CC=1.C1C=C[NH+]=CC=1.Br[Br-]Br.C1(O)C=CC=CC=1>C(OCC)(=O)C>[CH3:1][C@:2]12[CH2:18][CH2:17][C:16]3[C@@H:7]([CH2:8][CH2:9][C:10]4[C:15]=3[CH2:14][CH2:13][C:12](=[O:19])[CH:11]=4)[C@@H:6]1[CH2:5][CH:4]=[CH:3]2

Participants

5

Reactant 3

HCID 996PhenolHCID 1049PyridineHCID 15870993Estra-5(10),16-dien-3-one2×

Product 1

HCID 15870985Estra-4,9,16-trien-3-oneYield 31%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Estra-5(10),16-dien-3-one, 3 (0.38 g, 1.5 mmol), in pyridine (5.0 ml, 62 mmol) was cooled in an ice-salt bath to −13° C. and pyridinium bromide perbromide (1.58 g, 4.94 mmol) was added in small portions so that T<−4° C. After swirling 1 min. phenol (0.25 g, 2.7 mmol) was added and reaction continued 24 h at room temperature. See FIG. 12. Ethyl acetate (50 ml) was added and the reaction mixture was washed with 25 ml of 1N HCl, two 25 ml portions of saturated copper sulfate, 25 ml of 5% sodium hydroxide, and 25 ml of brine. After drying over magnesium sulfate, filtration, and concentration under reduced pressure the residue was taken up in 10 ml of abs. ethanol, granular zinc (0.33 g, 5.0 mg-atom) was added, and the mixture was refluxed ½ h. The supernatant was removed, the residue was washed with 10 ml of abs. ethanol, and the combined supernatants were concentrated under reduced pressure. The resulting resin was flash chromatographed on silica gel using 15% ethyl acetate/hexane as eluent. Appropriate fractions were pooled, concentrated, and then recrystallized from hexane to give solid product (117.5 mg, 0.4619 mmol, 31%), m.p. 87-92° C.

Workup

  1. customreaction continued 24 h at room temperature
  2. washthe reaction mixture was washed with 25 ml of 1N HCl, two 25 ml portions of saturated copper sulfate, 25 ml of 5% sodium hydroxide, and 25 ml of brine
  3. dry with materialAfter drying over magnesium sulfate, filtration, and concentration under reduced pressure the residue
  4. additionethanol, granular zinc (0.33 g, 5.0 mg-atom) was added
  5. temperaturethe mixture was refluxed ½ h
  6. customThe supernatant was removed
  7. washthe residue was washed with 10 ml of abs
  8. concentrationethanol, and the combined supernatants were concentrated under reduced pressure
  9. customchromatographed on silica gel using 15% ethyl acetate/hexane as eluent
  10. concentrationconcentrated
  11. customrecrystallized from hexane

Sources & evidence

ORD record
ord-193550752d8345c5adbd0cabc592c853
Source dataset
uspto-grants-2001_12
Patent number
US06331534B1

Reaction notes

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