Estradiol → 3-O-Benzyl Estradiol

HRID 2081173Notes

Reaction equation

HRID 2081173 reaction equation
[OH:1][C:2]1[CH:19]=[CH:18][C:17]2[C@@H:16]3[C@H:7]([C@H:8]4[C@@:12]([CH2:14][CH2:15]3)([CH3:13])[C@@H:11]([OH:20])[CH2:10][CH2:9]4)[CH2:6][CH2:5][C:4]=2[CH:3]=1.[H-].[Na+].[CH2:23](Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>CN(C=O)C>[CH2:23]([O:1][C:2]1[CH:19]=[CH:18][C:17]2[C@@H:16]3[C@H:7]([C@H:8]4[C@@:12]([CH2:14][CH2:15]3)([CH3:13])[C@@H:11]([OH:20])[CH2:10][CH2:9]4)[CH2:6][CH2:5][C:4]=2[CH:3]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

5

Reactant 3

HCID 5757EstradiolHCID 7498Benzyl BromideHCID 24758Sodium hydride

Product 1

HCID 112914133-O-Benzyl EstradiolYield 85.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 3,17β-dihydroxyestra-1,3,5(10)-triene (4.73 g, 17.4 mmol) in DMF (10 mL) was added slowly to a stirred and cooled mixture of 60% NaH (1.1 g, 27.5 mmol) in DMF (10 mL). After addition was complete, the cooling bath was removed and the mixture stirred at room temperature for 1 hour until all of the NaH had reacted. Benzyl bromide (2.9 mL, 27.8 mmol) was added in a stream and the solution stirred at room temperature for 20 hours. After concentrating under reduced pressure, the residue was partitioned between EtOAc and 10% citric acid. The aqueous layer was extracted with EtOAc again and the organic extracts combined, washed with saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The residue was triturated with Et2O-hexane to give 5.38 g (85%) of the above-titled product, mp=97°-100°.

Workup

  1. temperaturecooled
  2. additionAfter addition
  3. customthe cooling bath was removed
  4. stirringthe mixture stirred at room temperature for 1 hour until all of the NaH
  5. customhad reacted
  6. stirringthe solution stirred at room temperature for 20 hours
  7. concentrationAfter concentrating under reduced pressure
  8. customthe residue was partitioned between EtOAc and 10% citric acid
  9. extractionThe aqueous layer was extracted with EtOAc again
  10. washwashed with saturated NaHCO3 solution
  11. dry with materialdried (Na2SO4)
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe residue was triturated with Et2O-hexane

Sources & evidence

ORD record
ord-5d1efb08b3bc488094cbdb0b8adad44a
Source dataset
uspto-grants-1993_02
Patent number
US05183815

Reaction notes

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