Azobisisobutyronitrile → 1alpha,3beta-bis(tert-butyldimethylsilyloxy)-20(S)-hydroxypregna-5,7,16-triene

HRID 1510967Notes

Reaction equation

HRID 1510967 reaction equation
[Si:1]([O:8][C@@H:9]1[C@@:28]2([CH3:29])[C:13](=[CH:14][CH2:15][C@@H:16]3[C@@H:27]2[CH2:26][CH2:25][C@@:24]2([CH3:30])[C@H:17]3[CH2:18][CH2:19][C@:20]32[O:23][C@H:21]3[CH3:22])[CH2:12][C@@H:11]([O:31][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].N(C(C)(C)C#N)=NC(C)(C)C#N.CC1C=C(C)N=C(C)C=1>CCCCCCC>[Si:1]([O:8][C@@H:9]1[C@@:28]2([CH3:29])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:27]2[CH2:26][CH2:25][C@@:24]2([CH3:30])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C@@H:21]([OH:23])[CH3:22])[CH2:12][C@@H:11]([O:31][Si:32]([C:35]([CH3:36])([CH3:38])[CH3:37])([CH3:33])[CH3:34])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6547AzobisisobutyronitrileHCID 79532,4,6-TrimethylpyridineHCID 86646628HCID 86646628, compound

Product 1

HCID 120200781alpha,3beta-bis(tert-butyldimethylsilyloxy)-20(S)-hydroxypregna-5,7,16-trieneYield 37.7%

Reagents, catalysts & solvents 1

HCID 8900HeptaneSolvent

Procedure

To (1S,3R,17R,20S)-1,3-bis(tert-butyldimethylsilyloxy)-17,20-epoxypregna-5-ene (100 g) obtained in Example 1, 2,2′-azobis(isobutyronitrile) (7.98 g) and γ-collidine (82.4 mL) were added, and the resulting mixture was stirred in n-heptane (1000 mL) at 75° C. for 15 minutes. After cooling the mixture to room temperature, a precipitate was removed by filtration, and the filtrate which was a solution in n-heptane was concentrated under reduced pressure. To the obtained concentrated residue containing γ-collidine, toluene (650 mL) and aluminum isopropoxide (3.64 g) were added, and the resulting mixture was heated to reflux for 2 hours. The reaction solution was cooled, and the organic layer was sequentially washed with aqueous hydrochloric acid, aqueous sodium bicarbonate and with water, followed by concentration under reduced pressure. After suspending the obtained concentrated residue in a mixed solvent of ethyl acetate, acetonitrile and triethylamine, a precipitate was collected by filtration, washed with acetonitrile, heat-dried under reduced pressure to obtain (1S,3R,20S)-1,3-bis(tert-butyldimethylsilyloxy)-20-hydroxypregna-5,7,16-triene as slightly yellow powder (37.5 g; yield: 37.7%).

Workup

  1. customa precipitate was removed by filtration
  2. concentrationwas concentrated under reduced pressure
  3. additionTo the obtained concentrated residue containing γ-collidine, toluene (650 mL) and aluminum isopropoxide (3.64 g)
  4. additionwere added
  5. temperaturethe resulting mixture was heated
  6. temperatureto reflux for 2 hours
  7. temperatureThe reaction solution was cooled
  8. washthe organic layer was sequentially washed with aqueous hydrochloric acid, aqueous sodium bicarbonate and with water
  9. concentrationfollowed by concentration under reduced pressure
  10. filtrationa precipitate was collected by filtration
  11. washwashed with acetonitrile
  12. customheat-dried under reduced pressure

Sources & evidence

ORD record
ord-cae1583ccf4c497ea1a276500230b088
Source dataset
uspto-grants-2012_07
Patent number
US08212059B2

Reaction notes

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