Hydrogen Peroxide → (2R)-11-(17beta-hydroxy-3-methoxyestra-1,3,5(10)-trien-7alpha-yl)-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)undecanoic acid

HRID 460487Notes

Reaction equation

HRID 460487 reaction equation
[CH3:1][N:2]1[C@@H:6]([CH3:7])[C@@H:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:4]([C:14](=[O:61])[C@@H:15]([CH2:46][CH2:47][C:48]([F:60])([F:59])[C:49]([F:58])([F:57])[C:50]([F:56])([F:55])[C:51]([F:54])([F:53])[F:52])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C@@H:25]2[CH2:42][C:41]3[CH:40]=[C:39]([O:43][CH3:44])[CH:38]=[CH:37][C:36]=3[C@@H:35]3[C@@H:26]2[C@H:27]2[C@@:31]([CH2:33][CH2:34]3)([CH3:32])[C@@H:30]([OH:45])[CH2:29][CH2:28]2)[C:3]1=[O:62].[OH-:63].C([N+](CCCC)(CCCC)CCCC)CCC.OO>COCCOC>[OH:45][C@H:30]1[CH2:29][CH2:28][C@H:27]2[C@H:26]3[C@H:35]([CH2:34][CH2:33][C@:31]12[CH3:32])[C:36]1[CH:37]=[CH:38][C:39]([O:43][CH3:44])=[CH:40][C:41]=1[CH2:42][C@H:25]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][C@H:15]([CH2:46][CH2:47][C:48]([F:59])([F:60])[C:49]([F:58])([F:57])[C:50]([F:56])([F:55])[C:51]([F:52])([F:53])[F:54])[C:14]([OH:61])=[O:63].[CH3:1][N:2]1[C@@H:6]([CH3:7])[C@@H:5]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[NH:4][C:3]1=[O:62]

Participants

6

Reactant 3

HCID 784Hydrogen PeroxideHCID 2723671Tetrabutylammonium HydroxideHCID 86588682(4S,5R)-3,4-dimethyl-1-[(2R)-11-(17beta-hydroxy-3-methoxyestra-1,3,5(10)-trien-7alpha-yl)-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)undecanoyl]-5-phenylimidazolidin-2-one

Product 2

HCID 6931391(4R,5S)-(-)-1,5-Dimethyl-4-phenyl-2-imidazolidinoneYield 98%HCID 86588539(2R)-11-(17beta-hydroxy-3-methoxyestra-1,3,5(10)-trien-7alpha-yl)-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)undecanoic acidYield 100%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
0 °C

Procedure

(4S,5R)-3,4-Dimethyl-1-[(2R)-11-(17β-hydroxy-3-methoxyestra-1,3,5(10)-trien-7α-yl)-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)undecanoyl]-5-phenylimidazolidin-2-one (445 mg, 0.50 mmol) was dissolved in anhydrous ethylene glycol dimethyl ether (5 ml) under nitrogen atmosphere and then cooled to 0° C. To this solution, tetra-n-butylammonium hydroxide solution (40% w/w, 649 mg, 1.0 mmol) and aqueous hydrogen peroxide (30% w/w, 113 mg, 1.0 mmol) were added, and the resulting mixture was stirred for 1.5 hours at room temperature. The reaction mixture was quenched with saturated aqueous sodium thiosulfate, acidified with saturated aqueous potassium bisulfate, and then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure using an evaporator and the resulting residue was purified by silica gel column chromatography (Wako gel C-200, eluent: ethyl acetate/n-hexane=4/6→8/2) to give (2R)-11-(17β-hydroxy-3-methoxyestra-1,3,5(10)-trien-7α-yl)-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)undecanoic acid (360 mg, Yield 100%) and (4R,5S)-1,5-dimethyl-4-phenylimidazolidin-2-one (93 mg, Yield 98%).

Workup

  1. customThe reaction mixture was quenched with saturated aqueous sodium thiosulfate
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customan evaporator
  8. customthe resulting residue was purified by silica gel column chromatography (Wako gel C-200, eluent: ethyl acetate/n-hexane=4/6→8/2)

Sources & evidence

ORD record
ord-a0b50de87d8447199e95431429ee3f4d
Source dataset
uspto-grants-2007_03
Patent number
US07196081B2

Reaction notes

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