Ethyl isocyanate → (11beta,16beta)-21-(Acetyloxy)-9-fluoro-16-methyl-3,20-dioxo-11-[(trimethylsilyl)-oxy]pregna-1,4-dien-17-yl ethylcarbamate

HRID 14374Notes

Reaction equation

HRID 14374 reaction equation
[C:1]([O:4][CH2:5][C:6](=[O:35])[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]([CH3:30])([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].[CH2:36]([N:38]=[C:39]=[O:40])[CH3:37].COC(C)(C)C.CCCCCC.C(Cl)(Cl)Cl>C1(C)C=CC=CC=1>[CH2:36]([NH:38][C:39](=[O:40])[O:34][C@:7]1([C@:24]2([CH3:25])[C@H:10]([C@H:11]3[C@:21]([F:31])([C@@H:22]([O:26][Si:27]([CH3:28])([CH3:30])[CH3:29])[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])[C:6](=[O:35])[CH2:5][O:4][C:1](=[O:3])[CH3:2])[CH3:37]

Participants

5

Reactant 3

HCID 8022Ethyl isocyanateHCID 11352672(11beta,16beta)-9-Fluoro-17-hydroxy-16-methyl-3,20-dioxo-11-[(trimethyl-silyl)oxy]-pregna-1,4-dien-21-yl acetateHCID 131728161t-Butyl methyl ether hexane chloroform

Product 1

HCID 68717367(11beta,16beta)-21-(Acetyloxy)-9-fluoro-16-methyl-3,20-dioxo-11-[(trimethylsilyl)-oxy]pregna-1,4-dien-17-yl ethylcarbamateYield 62.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a mixture of (11β,16β)-9-fluoro-17-hydroxy-16-methyl-3,20-dioxo-11-[(trimethyl-silyl)oxy]-pregna-1,4-dien-21-yl acetate (3.11 g, 6.15 mmol) in 41 mL of toluene was added neat ethyl isocyanate (20.5 mL, 259 mmol) and the mixture was refluxed for 48 hours. The resulting solution was cooled to room temperature and evaporated under vacuum to leave a slightly gummy solid. Flash chromatography through a 1 kg column of silica gel eluting with t-butyl methyl ether/hexane/chloroform (1:1:1) gave 2.22 g of the title compound as a white solid.

Workup

  1. temperaturethe mixture was refluxed for 48 hours
  2. customevaporated under vacuum
  3. customto leave a slightly gummy solid

Sources & evidence

ORD record
ord-a6663e1989114dada27ab5d109dc064c
Source dataset
uspto-grants-2010_06
Patent number
US07732432B2

Reaction notes

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