Imidazole → (1alpha,3beta)-3-[[Dimethyl(1,1,2-trimethylpropyl)silyl]oxy]-1-[(triethylsilyl)oxy]androsta-5,7-dien-17-one

HRID 481810

Reaction equation

HRID 481810 reaction equation
[OH:1][C@@H:2]1[C@@:19]2([CH3:20])[C:6](=[CH:7][CH:8]=[C:9]3[C@@H:18]2[CH2:17][CH2:16][C@@:14]2([CH3:15])[C@H:10]3[CH2:11][CH2:12][C:13]2=[O:21])[CH2:5][C@@H:4]([OH:22])[CH2:3]1.N1C=CN=C1.[C:28]([Si:34](Cl)([CH3:36])[CH3:35])([CH:31]([CH3:33])[CH3:32])([CH3:30])[CH3:29].[CH2:38]([Si:40](Cl)([CH2:43][CH3:44])[CH2:41][CH3:42])[CH3:39]>CCCCCC.ClCCl>[CH3:35][Si:34]([CH3:36])([C:28]([CH3:30])([CH3:29])[CH:31]([CH3:33])[CH3:32])[O:22][C@H:4]1[CH2:3][C@H:2]([O:1][Si:40]([CH2:43][CH3:44])([CH2:41][CH3:42])[CH2:38][CH3:39])[C@@:19]2([CH3:20])[C:6](=[CH:7][CH:8]=[C:9]3[C@@H:18]2[CH2:17][CH2:16][C@@:14]2([CH3:15])[C@H:10]3[CH2:11][CH2:12][C:13]2=[O:21])[CH2:5]1

Participants

7

Reactant 4

HCID 795ImidazoleHCID 13819ChlorotriethylsilaneHCID 144239Dimethylthexylsilyl chlorideHCID 53733170(1alpha,3beta)-1,3-Dihydroxyandrosta-5,7-dien-17-one

Product 1

HCID 86752998(1alpha,3beta)-3-[[Dimethyl(1,1,2-trimethylpropyl)silyl]oxy]-1-[(triethylsilyl)oxy]androsta-5,7-dien-17-oneYield 87%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8058HexaneSolvent

Procedure

A 3-L three-necked flask equipped with a mechanical stirrer, addition funnel, and Ar-inlet tube was charged with 60.1 g (199 mmol) of (1α,3β)-1,3-dihydroxyandrosta-5,7-dien-17-one, 40.7 g (598 mmol) of imidazole, and 400 mL of dichloromethane. After cooling with an ice-water bath for 5 min., 50.7 mL (257 mmol) of thexyldimethylsilyl chloride was added over 12 min. The cold bath was removed, and the mixture was stirred at room temperature for 5 hr. After cooling again with an ice-water bath. 36.8 mL (219 mmol) of triethylsilyl chloride was added over 10 min. After stirring at room temperature overnight, 220 mL of hexane was added. After 15 min, the precipitate was removed by filtration and washed with 2×120 mL of hexane. The combined filtrate and washes were concentrated, and the residual hexane was removed by co-evaporation with 120 mL of methanol, and the suspension was stirred for 2 hr in order to obtain a powdery material. After the suspension was stored in a refrigerator overnight, the precipitate was filtered and washed with 2×160 mL of 95% methanol. Drying under high vacuum afforded 96.8 g of (1α,3β)-3-[[dimethyl(1,1,2-trimethylpropyl)silyl]oxy]-1-[(triethylsilyl)oxy]androsta-5,7-dien-17-one as a beige solid.

Workup

  1. customA 3-L three-necked flask equipped with a mechanical stirrer, addition funnel
  2. temperatureAfter cooling with an ice-water bath for 5 min.
  3. customThe cold bath was removed
  4. temperatureAfter cooling again with an ice-water bath
  5. stirringAfter stirring at room temperature overnight
  6. waitAfter 15 min
  7. customthe precipitate was removed by filtration
  8. washwashed with 2×120 mL of hexane
  9. concentrationThe combined filtrate and washes were concentrated
  10. customthe residual hexane was removed by co-evaporation with 120 mL of methanol
  11. stirringthe suspension was stirred for 2 hr in order
  12. customto obtain a powdery material
  13. customwas stored in a refrigerator overnight
  14. filtrationthe precipitate was filtered
  15. washwashed with 2×160 mL of 95% methanol
  16. customDrying under high vacuum

Sources & evidence

ORD record
ord-4030b800772b4608ad0f7d86915fe367
Source dataset
uspto-grants-1998_08
Patent number
US05789607

Linked notes

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