Cyclohexanone → HCID 67279572, compound

HRID 1781988Notes

Reaction equation

HRID 1781988 reaction equation
[CH3:1][C@@:2]12[C@@H:18]([OH:19])[CH2:17][CH2:16][C@H:15]1[C@H:14]1[C@@H:5]([C:6]3[C:11]([CH2:12][CH2:13]1)=[CH:10][C:9](O)=[C:8]([O:21][CH3:22])[CH:7]=3)[CH2:4][CH2:3]2.CC(C)[O-].[Al+3].CC(C)[O-].CC(C)[O-].C1(=O)CCCCC1>C(=O)(O)[O-].[Na+]>[CH3:22][O:21][C:8]1[CH:9]=[CH:10][C:11]2[CH2:12][CH2:13][C@@H:14]3[C@@H:5]([C:6]=2[CH:7]=1)[CH2:4][CH2:3][C@@:2]1([CH3:1])[C@H:15]3[CH2:16][CH2:17][C:18]1=[O:19]

Participants

5

Reactant 3

HCID 7967CyclohexanoneHCID 11143Aluminum isopropoxideHCID 664142-Methoxyestradiol2×

Product 1

HCID 67279572HCID 67279572, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

2-Methoxyestradiol (Scheme 1, Compound 1) (10 g, 33.1 mmol) was placed in a 1 L round bottom flask that was equipped with a 25 mL Dean-Stark trap and a reflux condenser. The entire apparatus had been flame dried under an argon atmosphere. Toluene (400 mL) was added to dissolve the starting material. Aluminum isopropoxide (34.6 g, 169 mmol) and cyclohexanone (135 mL, 1.3 mol) were added and the entire reaction mixture was heated at reflux (145°-150° C.) for 20 h. Saturated aqueous sodium bicarbonate solution (200 mL) was added after the reaction mixture was allowed to cool to room temperature. The organic material was extracted with dichloromethane (3×300 mL). The aqueous emulsion was acidified with 3 N HCl (˜20 mL) until the emulsion separated and the aqueous layer was extracted with ethyl acetate (2×75 mL). The combined organic extracts were dried over magnesium sulfate and condensed using a rotary evaporator. The cyclohexanone and cyclohexanol were removed by vacuum distillation. When the distillation pot was cool enough, hexane was added and 2-methoxyestrone (Scheme 1, Compound 4) precipitated out of solution. 7.72 g (25.7 mmol, 78%) of product was obtained. 1H NMR (300 MHz, CDCl3) δ 6.81 (s, 1H), 6.68 (s, 1H), 5.46 (s, 1H), 3.88 (s, 3H), 2.89-2.76 (m,2H), 2.61-1.24 (m, 13H), 0.94 (s, 3H).

Workup

  1. customthat was equipped with a 25 mL Dean-Stark trap and a reflux condenser
  2. temperatureThe entire apparatus had been flame
  3. customdried under an argon atmosphere
  4. additionToluene (400 mL) was added
  5. dissolutionto dissolve the starting material
  6. customthe entire reaction mixture
  7. temperaturewas heated
  8. temperatureat reflux (145°-150° C.) for 20 h
  9. extractionThe organic material was extracted with dichloromethane (3×300 mL)
  10. customseparated
  11. extractionthe aqueous layer was extracted with ethyl acetate (2×75 mL)
  12. dry with materialThe combined organic extracts were dried over magnesium sulfate and condensed
  13. customa rotary evaporator
  14. customThe cyclohexanone and cyclohexanol were removed by vacuum distillation
  15. temperatureWhen the distillation pot was cool enough
  16. additionhexane was added
  17. custom2-methoxyestrone (Scheme 1, Compound 4) precipitated out of solution

Sources & evidence

ORD record
ord-7711a63c29b94a50b0c1d8924e8d79e6
Source dataset
uspto-grants-2009_03
Patent number
US07498322B2

Reaction notes

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