Reaction #42651

Reaction equation

acetic acid

(11β,16β)-9-fluoro-16-methyl-3,20-dioxo-11,17-bis[(trimethylsilyl)oxy]pregna-1,4-dien-21-yl acetate

tetra-n-butylammonium fluoride

→

title compound

Yield 73.9%

(11β,16β)-9-fluoro-17-hydroxy-16-methyl-3,20-dioxo-11-[(trimethylsilyl)oxy]-pregna-1,4-dien-21-yl acetate

Yield 73.9%

Solvents

tetrahydrofuran

THF

Conditions

Workup

1. 1
   Otherthe ice bath was removed
2. 2
   Temperatureto warm to room temperature
3. 3
   workup.STIRRINGstir for an additional 16 hours
4. 4
   OtherMost of the THF was removed by rotary evaporation in vacuo
5. 5
   Otherthe residue was partitioned between ethyl acetate and water
6. 6
   WashThe organic layer was washed successively with water, sat. NH4Cl, water, sat. NaHCO3, water and brine
7. 7
   DryingThe organic layer was dried over Na2SO4
8. 8
   Filtrationfiltered
9. 9
   Otherevaporated under vacuum
10. 10
    Otherto give an off-white solid
11. 11
    OtherPurification by flash chromatography through a 1.6 kg column of silica gel eluting with 4% MeOH in dichloromethane

Procedure

A solution of (11β,16β)-9-fluoro-16-methyl-3,20-dioxo-11,17-bis[(trimethylsilyl)oxy]pregna-1,4-dien-21-yl acetate (26 g, ˜43 mmol) in 430 mL of tetrahydrofuran (THF) was cooled to 0° C. and neat acetic acid (4.95 mL, 86.5 mmol) was added followed by dropwise addition of a 1.0 M solution of tetra-n-butylammonium fluoride in THF (43.3 mL, 43.3 mmol). After stirring at 0° C. for 4 hours, the ice bath was removed and the reaction was allowed to warm to room temperature and stir for an additional 16 hours. Most of the THF was removed by rotary evaporation in vacuo and the residue was partitioned between ethyl acetate and water. The organic layer was washed successively with water, sat. NH4Cl, water, sat. NaHCO3, water and brine. The organic layer was dried over Na2SO4, filtered and evaporated under vacuum to give an off-white solid. Purification by flash chromatography through a 1.6 kg column of silica gel eluting with 4% MeOH in dichloromethane provided 16.1 g of the title compound as a white solid.

Source