Estra-1,3,5(10),16-tetraen-3-ol → Estra-1,3,5(10),6,8,16-hexaen-3-ol

HRID 1107201Notes

Reaction equation

HRID 1107201 reaction equation
C([Li])CCC.[CH3:6][C@:7]12[CH2:23][CH2:22][C@H:21]3[C@@H:12]([CH2:13][CH2:14][C:15]4[CH:16]=[C:17]([OH:24])[CH:18]=[CH:19][C:20]=43)[C@@H:11]1[CH2:10][CH:9]=[CH:8]2>C1COCC1>[CH3:6][C@:7]12[CH2:23][CH2:22][C:21]3[C:20]4[CH:19]=[CH:18][C:17]([OH:24])=[CH:16][C:15]=4[CH:14]=[CH:13][C:12]=3[C@@H:11]1[CH2:10][CH:9]=[CH:8]2

Participants

4

Reactant 2

HCID 101988Estra-1,3,5(10),16-tetraen-3-olHCID 178418339Butyllithium

Product 1

HCID 54020244Estra-1,3,5(10),6,8,16-hexaen-3-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a cooled (ice water bath) solution of crude estra-1,3,5(10)6,8-pentaen-3-ol 17-(p-toluenesuffonyl)hydrozone (7, 1.0887 g, ≤2463 mmol) in anh. THF (25 ml) under argon was added n-butyllithium (2.5 M in hexane, 3.9 ml, 9.8 mmol) dropwise with stirring over 2 min. See FIG. 159. Stirring was continued 3 days, during which the reaction was allowed to gradually warm to room temperature. 50 ml of 1 hydrochloric acid-ice were added and the mixture was extracted three times with 25 ml portions of ether. The combined organic extracts were washed with 50 ml of brine, dried over magnesium sulfate, and filtered through diatomaceous earth. The residue was washed 10 ml of ether and the combined filtrates were concentrated under reduced pressure. Flash chromatography (20% ethyl acetate/hexanes on silica gel) and recrystallization from aqueous ethanol with charcoal decolorization gave tan platelets (245.8 mg, 0.9819 mmol, 40%), m.p. 162-163° C.

Workup

  1. stirringStirring
  2. waitwas continued 3 days, during which
  3. extractionthe mixture was extracted three times with 25 ml portions of ether
  4. washThe combined organic extracts were washed with 50 ml of brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered through diatomaceous earth
  7. washThe residue was washed 10 ml of ether
  8. concentrationthe combined filtrates were concentrated under reduced pressure
  9. customFlash chromatography (20% ethyl acetate/hexanes on silica gel) and recrystallization from aqueous ethanol with charcoal decolorization
  10. customgave tan platelets (245.8 mg, 0.9819 mmol, 40%), m.p. 162-163° C.

Sources & evidence

ORD record
ord-a5f31c848d4846e081bb634c9ae73ff8
Source dataset
uspto-grants-2000_05
Patent number
US06057439

Reaction notes

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