Dehydroepiandrosterone → 7-Oxodehydroepiandrosterone 3-acetate

HRID 650698

Reaction equation

HRID 650698 reaction equation
[CH3:1][C@@:2]12[C:10](=[O:11])[CH2:9][CH2:8][C@H:7]1[C@@H:6]1[CH2:12][CH:13]=[C:14]3[CH2:19][C@@H:18]([OH:20])[CH2:17][CH2:16][C@:15]3([CH3:21])[C@H:5]1[CH2:4][CH2:3]2.[C:22]([O:26]O)(C)(C)[CH3:23].Cl[O-:29].[Na+]>C(OCC)(=O)C>[C:22]([O:20][C@H:18]1[CH2:17][CH2:16][C@@:15]2([CH3:21])[C:14](=[CH:13][C:12](=[O:29])[C@@H:6]3[C@@H:5]2[CH2:4][CH2:3][C@@:2]2([CH3:1])[C@H:7]3[CH2:8][CH2:9][C:10]2=[O:11])[CH2:19]1)(=[O:26])[CH3:23]

Participants

5

Reactant 3

HCID 5881DehydroepiandrosteroneHCID 6410tert-Butyl hydroperoxideHCID 23665760Sodium Hypochlorite

Product 1

HCID 97982297-Oxodehydroepiandrosterone 3-acetate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
2.5 °C

Procedure

The above solution of DHEA-Ac (2) in ethyl acetate (˜1000 ml) was taken in a 5L three necked flask fitted with a thermometer and a pressure equalizing dropping funnel. An aqueous solution of tert-butyl hydroperoxide (70% aqueous solution from Aldrich, 270 ml, 6.0 equivalents) was added and the mixture was cooled to 0-5° C. Aqueous sodium hypochlorite solution (950 ml, 5.25% solution, purchased as house hold bleach) was added dropwise under good stirring to the cooled solution during a period of ten hours at 0-5° C. After completion of addition, the lower aqueous layer was removed and the organic (ethyl acetate) layer was stirred with sodium sulfite solution (100.0 gm in 300 ml of water) for 3 hours at 40-45° C. The aqueous yellow layer was removed and the organic layer was washed twice with 100 ml of half saturated brine, dried over anhydrous magnesium sulfate and concentrated to 50 ml volume. On triturating with hexane, 3β-acetoxyandrost-5-en-7,17-dione (7-oxo-DHEA-Ac, 3) crystallized out as a white solid, yield 79.4 gm (66.5%, based on DHEA), purity (HPLC) 98.86%. The resulting solid was recrystallized from ethanol, providing 3β-acetoxyandrost-5-en-7,17-dione (3) as white crystalline solid (70.0 gm, purity (HPLC) 99.8%, melting point 185-186° C.

Workup

  1. customfitted with a thermometer
  2. additionAfter completion of addition
  3. customthe lower aqueous layer was removed
  4. stirringthe organic (ethyl acetate) layer was stirred with sodium sulfite solution (100.0 gm in 300 ml of water) for 3 hours at 40-45° C
  5. customThe aqueous yellow layer was removed
  6. washthe organic layer was washed twice with 100 ml of half saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated to 50 ml volume
  9. customOn triturating with hexane, 3β-acetoxyandrost-5-en-7,17-dione (7-oxo-DHEA-Ac, 3)
  10. customcrystallized out as a white solid, yield 79.4 gm (66.5%, based on DHEA), purity (HPLC) 98.86%
  11. customThe resulting solid was recrystallized from ethanol

Sources & evidence

ORD record
ord-0161b5ff35a0427589b40424d8538dcd
Source dataset
uspto-grants-2001_08
Patent number
US06274746B1

Linked notes

Loading…