Tetrahydrofuran → Estra-1,3,5(10),16-tetraen-3,6-diol

HRID 1604742Notes

Reaction equation

HRID 1604742 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH3:7][C@:8]12[CH2:24][CH2:23][C@H:22]3[C@@H:13]([CH2:14][C:15](=[O:29])[C:16]4[CH:17]=[C:18](CC([O-])=O)[CH:19]=[CH:20][C:21]=43)[C@@H:12]1[CH2:11][CH:10]=[CH:9]2.C1C[O:33]CC1>>[CH3:7][C@:8]12[CH2:24][CH2:23][C@H:22]3[C@@H:13]([CH2:14][CH:15]([OH:29])[C:16]4[CH:17]=[C:18]([OH:33])[CH:19]=[CH:20][C:21]=43)[C@@H:12]1[CH2:11][CH:10]=[CH:9]2

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 21226445Aluminium lithium hydride2×HCID 22873077Estra-1,3,5(10),16-tetraen-6-one-3-yl-acetate

Product 1

HCID 15870995Estra-1,3,5(10),16-tetraen-3,6-diol

Procedure

To a suspension of lithium aluminum hydride (LAH, 95%, 46.9 mg, 1.17 mmol) in 5 mL of anhydrous THF was added estra-1,3,5(10),16-tetraen-6-one-3-yl-acetate (6) (422.9 mg, 1.360 mmol) in 5 mL of anhydrous THF dropwise, with stirring. The reaction was stirred 50 min., after which further LAH (46.5 mg, 1.16 mmol) was added and the reaction stirred 22 h. After refluxing 4 h TLC still showed starting material. The reaction was quenched with 0.5 mL of water +0.5 mL of 20% (w/w) sulfuric acid and concentrated under reduced pressure. The residue was extracted four times with 10 mL portions of hot ethyl acetate and filtered through Celite. The combined filtrates were concentrated and purified twice by flash chromatography to give solid product. (0.05 g, 0.2 mmol, 10%), m.p. 150-157° C.

Workup

  1. stirringThe reaction was stirred 50 min.
  2. stirringthe reaction stirred 22 h
  3. temperatureAfter refluxing 4 h TLC
  4. customThe reaction was quenched with 0.5 mL of water +0.5 mL of 20% (w/w) sulfuric acid
  5. concentrationconcentrated under reduced pressure
  6. extractionThe residue was extracted four times with 10 mL portions of hot ethyl acetate
  7. filtrationfiltered through Celite
  8. concentrationThe combined filtrates were concentrated
  9. custompurified twice by flash chromatography
  10. customto give solid product

Sources & evidence

ORD record
ord-739745f3996342cbbc641f0e573bc7bb
Source dataset
uspto-grants-1999_11
Patent number
US05994568

Reaction notes

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