Реакция #927367

Уравнение реакции

Ethylmagnesium chloride

3β-t-butyldimethylsilyloxy-androst-5,15-dien-17-one

3β-t-butyldimethylsilyloxy-androst-5,15(16)-dien-17-one

polyethylene

→

15β-ethyl-3β-t-butyldimethylsilyloxy-androst-5-en-17-one

Растворители

THF

THF

THF

Условия реакции

Обработка

1. 1
   Промывкаrinse (20 mL)
2. 2
   workup.STIRRINGThe reaction mixture is stirred for 2 hours at −22° C.
3. 3
   Температураto warm to ambient temperature over 30 minutes
4. 4
   workup.ADDITIONfollowed by addition of saturated aqueous NH4Cl (50 mL)
5. 5
   ЭкстракцияThe biphasic mixture is extracted with EtOAc (2×40 mL)
6. 6
   Промывкаthe combined organic layers are washed with brine (50 mL)
7. 7
   Сушкаdried over MgSO4
8. 8
   Фильтрацияfiltered
9. 9
   Другоеevaporated to dryness
10. 10
    ДругоеPurification by flash chromatography

Методика

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:

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