Acetic Acid → (11beta,16beta)-9-Fluoro-17-hydroxy-16-methyl-3,20-dioxo-11-[(trimethyl-silyl)oxy]-pregna-1,4-dien-21-yl acetate

HRID 14373Notes

Reaction equation

HRID 14373 reaction equation
[C:1]([O:4][CH2:5][C:6](=[O:39])[C@:7]1([O:34][Si](C)(C)C)[C@:24]2([CH3:25])[C@H:10]([C@H:11]3[C@:21]([F:31])([C@@H:22]([O:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[CH2:23]2)[C@:19]2([CH3:20])[C:14](=[CH:15][C:16](=[O:32])[CH:17]=[CH:18]2)[CH2:13][CH2:12]3)[CH2:9][C@@H:8]1[CH3:33])(=[O:3])[CH3:2].C(O)(=O)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[C:1]([O:4][CH2:5][C:6](=[O:39])[C@:7]1([OH:34])[C@:24]2([CH3:25])[C@H:10]([C@H:11]3[C@:21]([F:31])([C@@H:22]([O:26][Si:27]([CH3:29])([CH3:28])[CH3:30])[CH2:23]2)[C@:19]2([CH3:20])[C:14](=[CH:15][C:16](=[O:32])[CH:17]=[CH:18]2)[CH2:13][CH2:12]3)[CH2:9][C@@H:8]1[CH3:33])(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 2724141Tetrabutylammonium FluorideHCID 68714262(11beta,16beta)-9-Fluoro-16-methyl-3,20-dioxo-11,17-bis[(trimethylsilyl)oxy]pregna-1,4-dien-21-yl acetate

Product 1

HCID 11352672(11beta,16beta)-9-Fluoro-17-hydroxy-16-methyl-3,20-dioxo-11-[(trimethyl-silyl)oxy]-pregna-1,4-dien-21-yl acetateYield 73.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

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.

Workup

  1. customthe ice bath was removed
  2. temperatureto warm to room temperature
  3. stirringstir for an additional 16 hours
  4. customMost of the THF was removed by rotary evaporation in vacuo
  5. customthe residue was partitioned between ethyl acetate and water
  6. washThe organic layer was washed successively with water, sat. NH4Cl, water, sat. NaHCO3, water and brine
  7. dry with materialThe organic layer was dried over Na2SO4
  8. filtrationfiltered
  9. customevaporated under vacuum
  10. customto give an off-white solid
  11. customPurification by flash chromatography through a 1.6 kg column of silica gel eluting with 4% MeOH in dichloromethane

Sources & evidence

ORD record
ord-0a8c163b372448ffabb1d46cac6b07e3
Source dataset
uspto-grants-2010_06
Patent number
US07732432B2

Reaction notes

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