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

HRID 14372Notes

Reaction equation

HRID 14372 reaction equation
[C:1]([O:4][CH2:5][C:6](=[O:31])[C@:7]1([OH:30])[C@:24]2([CH3:25])[C@H:10]([C@H:11]3[C@:21]([F:27])([C@@H:22]([OH:26])[CH2:23]2)[C@:19]2([CH3:20])[C:14](=[CH:15][C:16](=[O:28])[CH:17]=[CH:18]2)[CH2:13][CH2:12]3)[CH2:9][C@@H:8]1[CH3:29])(=[O:3])[CH3:2].N1C=CN=C1.[CH3:37][Si:38](Cl)([CH3:40])[CH3:39]>CN(C)C=O.C(OCC)(=O)C>[C:1]([O:4][CH2:5][C:6](=[O:31])[C@:7]1([O:30][Si:38]([CH3:40])([CH3:39])[CH3:37])[C@:24]2([CH3:25])[C@H:10]([C@H:11]3[C@:21]([F:27])([C@@H:22]([O:26][Si:38]([CH3:40])([CH3:39])[CH3:37])[CH2:23]2)[C@:19]2([CH3:20])[C:14](=[CH:15][C:16](=[O:28])[CH:17]=[CH:18]2)[CH2:13][CH2:12]3)[CH2:9][C@@H:8]1[CH3:29])(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 795ImidazoleHCID 6397ChlorotrimethylsilaneHCID 443967Betamethasone acetate

Product 1

HCID 68714262(11beta,16beta)-9-Fluoro-16-methyl-3,20-dioxo-11,17-bis[(trimethylsilyl)oxy]pregna-1,4-dien-21-yl acetateYield 103.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (11β,16β)-9-fluoro-11,17-dihydroxy-16-methyl-3,20-dioxopregna-1,4-dien-21-yl acetate (18.79 g, 43.25 mmol) and imidazole (58.89 g, 864.9 mmol) in 200 mL of dry N,N-dimethylformamide was added neat trimethylsilyl chloride (55.0 mL, 433 mmol) dropwise during 15 min. The resulting pale yellow solution was stirred at room temperature for 16 hours. The solution was diluted with ethyl acetate and washed successively with water, sat. NH4Cl, water, sat. NaHCO3, water, and brine. The organic phase was dried over Na2SO4, filtered and evaporated in vacuo to yield 26 g of the title compound as a pale yellow oil.

Workup

  1. washwashed successively with water, sat. NH4Cl, water, sat. NaHCO3, water, and brine
  2. dry with materialThe organic phase was dried over Na2SO4
  3. filtrationfiltered
  4. customevaporated in vacuo

Sources & evidence

ORD record
ord-142febcdf4674e9da0f8a28df09f76de
Source dataset
uspto-grants-2010_06
Patent number
US07732432B2

Reaction notes

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