Imidazole → (3beta)-3-[[(1,1,2-Trimethylpropyl)dimethylsilyl]-oxy]androsta-5,7-dien-17-one

HRID 275508

Reaction equation

HRID 275508 reaction equation
[OH:1][C@H:2]1[CH2:19][CH2:18][C@@:17]2([CH3:20])[C:4](=[CH:5][CH:6]=[C:7]3[C@@H:16]2[CH2:15][CH2:14][C@@:12]2([CH3:13])[C@H:8]3[CH2:9][CH2:10][C:11]2=[O:21])[CH2:3]1.N1C=CN=C1.[CH3:27][Si:28](Cl)([CH3:35])[C:29]([CH:32]([CH3:34])[CH3:33])([CH3:31])[CH3:30]>ClCCl>[CH3:30][C:29]([Si:28]([CH3:35])([CH3:27])[O:1][C@H:2]1[CH2:19][CH2:18][C@@:17]2([CH3:20])[C:4](=[CH:5][CH:6]=[C:7]3[C@@H:16]2[CH2:15][CH2:14][C@@:12]2([CH3:13])[C@H:8]3[CH2:9][CH2:10][C:11]2=[O:21])[CH2:3]1)([CH3:31])[CH:32]([CH3:34])[CH3:33]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 144239Dimethylthexylsilyl chlorideHCID 117787743-Hydroxyandrosta-5,7-dien-17-one

Product 1

HCID 10320409(3beta)-3-[[(1,1,2-Trimethylpropyl)dimethylsilyl]-oxy]androsta-5,7-dien-17-oneYield 82.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
3 °C

Procedure

After a mixture of 149.9 g (523 mmol) (3β)-3-hydroxy-androsta-5,7-dien-17-one and 56.9 g (836 mmol) imidazole in 500 mL of dichloromethane was cooled to 3° C., 144 mL (732 mmol) dimethylthexylsilyl chloride was added dropwise over 90 min, keeping the temperature below 6° C. After stirring at room temperature overnight, the mixture was washed with 500 mL of water, and the aqueous layer was back-extracted with 200 mL of dichloromethane. The combined organic layers were washed with 500 mL of saturated aqueous NaHCO3, dried over sodium sulfate, and concentrated. The resulting solid was suspended in 700 mL of methanol containing 14 mL of triethylamine, and the suspension was refluxed for 20 minutes. After cooling in a refrigerator overnight, the precipitate was filtered, washed with 600 mL of methanol/H2O (9:1), and dried by suction for 2 hr. Further drying at 40° C. under high vacuum afforded 185.1 g (82.5% yield) of (3β)-3-[[(1,1,2-trimethylpropyl)dimethylsilyl]oxy]androsta-5,7-dien-17-one as a beige solid: mp 119°-125° C.; Anal. Calcd for C27H44O2Si: C, 75.64; H, 10.34; Si, 6.55. Found C, 75.82; H, 10.29; Si, 6.72.

Workup

  1. customthe temperature below 6° C
  2. washthe mixture was washed with 500 mL of water
  3. extractionthe aqueous layer was back-extracted with 200 mL of dichloromethane
  4. washThe combined organic layers were washed with 500 mL of saturated aqueous NaHCO3
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. temperaturethe suspension was refluxed for 20 minutes
  8. temperatureAfter cooling in a refrigerator overnight
  9. filtrationthe precipitate was filtered
  10. washwashed with 600 mL of methanol/H2O (9:1)
  11. customdried by suction for 2 hr
  12. customFurther drying at 40° C. under high vacuum

Sources & evidence

ORD record
ord-564762062c64400e9cb35a9c5fadee32
Source dataset
uspto-grants-1995_02
Patent number
US05393900

Linked notes

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