HCID 12149919, compound → HCID 70145734, compound

HRID 840185Notes

Reaction equation

HRID 840185 reaction equation
[CH2:1]([Mg]Cl)[CH3:2].[Si:5]([O:12][C@H:13]1[CH2:30][CH2:29][C@@:28]2([CH3:31])[C:15](=[CH:16][CH2:17][C@@H:18]3[C@@H:27]2[CH2:26][CH2:25][C@@:23]2([CH3:24])[C@H:19]3[CH:20]=[CH:21][C:22]2=[O:32])[CH2:14]1)([C:8]([CH3:11])([CH3:10])[CH3:9])([CH3:7])[CH3:6]>C1COCC1>[CH2:1]([C@H:20]1[C@H:19]2[C@H:18]3[C@H:27]([CH2:26][CH2:25][C@:23]2([CH3:24])[C:22](=[O:32])[CH2:21]1)[C@:28]1([CH3:31])[C:15]([CH2:14][C@@H:13]([O:12][Si:5]([C:8]([CH3:11])([CH3:9])[CH3:10])([CH3:7])[CH3:6])[CH2:30][CH2:29]1)=[CH:16][CH2:17]3)[CH3:2]

Participants

5

Reactant 3

HCID 12149919HCID 12149919, compoundHCID 178435160HCID 178435160, compoundHCID 178461633HCID 178461633, compound

Product 1

HCID 70145734HCID 70145734, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-22 °C

Procedure

Cuprous chloride (CuCl, 0.7611 g, 7.689 mmol) is slurried in THF (40 mL) under nitrogen and then chilled to −22° C. with a dry ice/tetrachloroethylene bath. Ethylmagnesium chloride solution (2.00 M in ether; 22.0 mL, 44.0 mmol) is added to the cold cuprous chloride slurry and the dark solution is stirred for 90 minutes. A solution of 3β-t-butyldimethylsilyloxy-androst-5,15-dien-17-one (from Example 28C;) in THF (50 mL) is added dropwise via polyethylene cannula to the organometallic solution over 10 minutes, followed by a THF rinse (20 mL). The reaction mixture is stirred for 2 hours at −22° C. and then allowed to warm to ambient temperature over 30 minutes, followed by addition of saturated aqueous NH4Cl (50 mL). The biphasic mixture is extracted with EtOAc (2×40 mL) and the combined organic layers are washed with brine (50 mL), dried over MgSO4, filtered and evaporated to dryness. Purification by flash chromatography gives 15β-ethyl-3β-t-butyldimethylsilyloxy-androst-5-en-17-one, which is deprotected as in Example 19C to give the corresponding 3-alcohol, which is then oxidized as in Example 16D to obtain the title compound, which has the following formula:

Workup

  1. washrinse (20 mL)
  2. stirringThe reaction mixture is stirred for 2 hours at −22° C.
  3. temperatureto warm to ambient temperature over 30 minutes
  4. additionfollowed by addition of saturated aqueous NH4Cl (50 mL)
  5. extractionThe biphasic mixture is extracted with EtOAc (2×40 mL)
  6. washthe combined organic layers are washed with brine (50 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated to dryness
  10. customPurification by flash chromatography

Sources & evidence

ORD record
ord-64af345b7a694fa79e0b3b44618d1e68
Source dataset
uspto-grants-2002_04
Patent number
US06365597B1

Reaction notes

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