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

HRID 1014980Notes

Reaction equation

HRID 1014980 reaction equation
[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:21](=[O:23])[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].B1(C)OC(C2C=CC=CC=2)(C2C=CC=CC=2)[C@@H]2N1CCC2.CO>C1(C)C=CC=CC=1>[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 887MethanolHCID 9838490(R)-2-Methyl-CBS-oxazaborolidineHCID 120200821alpha,3beta-Bis(tert-butyldimethylsilyloxy)-20-oxopregna-5,7,16-triene

Product 1

HCID 120200781alpha,3beta-bis(tert-butyldimethylsilyloxy)-20(S)-hydroxypregna-5,7,16-trieneYield 89%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
-20 °C

Procedure

The (1α,3β)-1,3-bis((tert-butyl(dimethyl)silyl)oxy)pregna-5,7,16-trien-20-one synthesized in Example 24 (45.0 g) was dissolved in toluene (240 ml) and then cooled to −20° C., followed by stirring for 30 minutes. Borane-dimethylsulfide complex (22.9 ml) was added to the resulting solution at −20° C. and stirred for 5 minutes. A 1M toluene solution of (R)-2-methyl-CBS-oxazaborolidine (22.9 ml) was further added to the solution at −20° C. and stirred for 1 hour. Methanol was added to the reaction mixture, which was then extracted with ethyl acetate. The extracted solution was dried over anhydrous sodium sulfate and evaporated under reduced pressure to remove the solvent. The resulting residue was purified by silica gel column chromatography (liquid phase: hexane/ethyl acetate=9/1) to give the titled compound (23.3 g, yield 89%).

Workup

  1. additionBorane-dimethylsulfide complex (22.9 ml) was added to the resulting solution at −20° C.
  2. stirringstirred for 5 minutes
  3. stirringstirred for 1 hour
  4. extractionwas then extracted with ethyl acetate
  5. dry with materialThe extracted solution was dried over anhydrous sodium sulfate
  6. customevaporated under reduced pressure
  7. customto remove the solvent
  8. customThe resulting residue was purified by silica gel column chromatography (liquid phase: hexane/ethyl acetate=9/1)

Sources & evidence

ORD record
ord-da5bcc08717940889cf19ce5e5200b36
Source dataset
uspto-grants-2011_07
Patent number
US07985744B2

Reaction notes

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