Diethyl Ether → HCID 22983888, compound

HRID 1263478Notes

Reaction equation

HRID 1263478 reaction equation
[CH2:1]1[O:24][C:4]2([CH2:21][CH2:20][C@@:19]3([CH3:22])[C:6](=[CH:7][CH2:8][C@@H:9]4[C@@H:18]3[CH2:17][CH2:16][C@@:14]3([CH3:15])[C@H:10]4[CH2:11][CH2:12][C:13]3=[O:23])[CH2:5]2)[O:3][CH2:2]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Cl[Si](C)(C)C.CCOCC>C1COCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.ClCCl.C(#N)C>[CH2:2]1[O:3][C:4]2([CH2:21][CH2:20][C@@:19]3([CH3:22])[C:6](=[CH:7][CH2:8][C@@H:9]4[C@@H:18]3[CH2:17][CH2:16][C@@:14]3([CH3:15])[C@H:10]4[CH:11]=[CH:12][C:13]3=[O:23])[CH2:5]2)[O:24][CH2:1]1

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 6397ChlorotrimethylsilaneHCID 2733832Lithium HexamethyldisilazideHCID 10758834HCID 10758834, compound

Product 1

HCID 22983888HCID 22983888, compoundYield 71%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent2×HCID 21877088Acetonitrile methylene chlorideSolvent

Procedure

Under argon atmosphere, a solution of 5-androsten-3,17-dione 3-ethyleneketal 10 (4.95 g, 0.0150 mol) in anhydrous THF (150 mL) was cooled at 0° C. and treated with 1.0 M solution of lithium bis(trimethylsilyl)amide in THF (18 mL, 0.018 mol). The solution was stirred 20 min at room temperature, cooled at −78° C., and treated with chlorotrimethylsilane (2.24 mL, 0.0176 mol). The reaction was allowed to warm to room temperature, then evaporated. The residue was diluted with dichloromethane, washed two times with water and brine, dried over magnesium sulfate, filtered, and evaporated. A solution of the crude silylenol ether in a dichloromethane-acetonitrile 2-5 (140 mL) was treated with palladium acetate (4.04 g 0.0180 mol) and refluxed for 30 min. The reaction mixture was cooled to room temperature and evaporated. The black residue was purified by flash chromatography (hexanes-ethyl acetate 4-1) to provide the enone 44 (3.49 g, 71%): 1H NMR (300 MHz, CDCl3) δ 1.085 (s, 3H), 1.09 (s, 3H), 1.21-1.93 (m, 11H), 2.15 (dd, J=2.7 and J=14.1 Hz, 1H), 2.26-2.34 (m, 2H), 2.58 (d, J=14.1 Hz, 1H), 3.95 (m, 4H), 5.40 (d, J=5.1 Hz, 1H), 6.04 (dd, J=3.2 and J=6 Hz, 1H), 7.50 (d, J=5.8 Hz, 1H).

Workup

  1. temperaturecooled at −78° C.
  2. temperatureto warm to room temperature
  3. customevaporated
  4. additionThe residue was diluted with dichloromethane
  5. washwashed two times with water and brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. temperaturerefluxed for 30 min
  10. temperatureThe reaction mixture was cooled to room temperature
  11. customevaporated
  12. customThe black residue was purified by flash chromatography (hexanes-ethyl acetate 4-1)

Sources & evidence

ORD record
ord-c5dc3f886e574ce396a31a9132d7e6f9
Source dataset
uspto-grants-2003_04
Patent number
US06541463B1

Reaction notes

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