Hydrogen Peroxide → (2R)-11-[3,17beta-dihydroxyestra-1,3,5(10)-trien-11beta-yl]-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)undecanic Acid

HRID 460491Notes

Reaction equation

HRID 460491 reaction equation
[OH:1][C:2]1[CH:19]=[CH:18][C:17]2[C@@H:16]3[C@H:7]([C@H:8]4[C@@:12]([CH2:14][C@@H:15]3[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][C@H:29]([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])[C:30]([N:32]3[C@H](C5C=CC=CC=5)[C@H](C)N(C)C3=O)=[O:31])([CH3:13])[C@@H:11]([OH:61])[CH2:10][CH2:9]4)[CH2:6][CH2:5][C:4]=2[CH:3]=1.[OH-:62].C([N+](CCCC)(CCCC)CCCC)CCC.[OH:80]O.C[O:83]CCOC>>[C:30](#[N:32])[CH3:29].[OH2:1].[F:52][C:51]([F:54])([F:53])[C:50]([OH:80])=[O:62].[OH:62][C:2]1[CH:19]=[CH:18][C:17]2[C@@H:16]3[C@H:7]([C@H:8]4[C@@:12]([CH2:14][C@@H:15]3[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][C@H:29]([CH2:46][CH2:47][C:48]([F:59])([F:60])[C:49]([F:57])([F:58])[C:50]([F:56])([F:55])[C:51]([F:54])([F:52])[F:53])[C:30]([OH:83])=[O:31])([CH3:13])[C@@H:11]([OH:61])[CH2:10][CH2:9]4)[CH2:6][CH2:5][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 784Hydrogen PeroxideHCID 80711,2-DimethoxyethaneHCID 2723671Tetrabutylammonium HydroxideHCID 86588540(4S, 5R)-1-{(2R)-11-[3,17beta-Dihydroxyestra-1,3,5(10)-trien-11beta-yl]-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)-undecanoyl}-3,4-dimethyl-5-phenylimidazolidin-2-one

Product 2

HCID 22145617Water TFA acetonitrileHCID 131724433(2R)-11-[3,17beta-dihydroxyestra-1,3,5(10)-trien-11beta-yl]-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)undecanic AcidYield 52%

Procedure

(4S,5R)-1-{(2R)-11-[3,17β-Dihydroxyestra-1,3,5(10)-trien-11β-yl]-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)undecanoyl}-3,4-dimethyl-5-phenylimidazolidin-2-one (140 mg, 0.16 mmol) was dissolved in DME (3 ml). To this solution, tetra-n-butylammonium hydroxide solution (40% w/w, 312 mg, 0.48 mmol) and aqueous hydrogen peroxide (30% w/w, 56 mg, 0.48 mmol) were added, and the resulting mixture was stirred for 2 hours at room temperature. The reaction mixture was quenched with 10% aqueous sodium sulfite, acidified with 2N hydrochloric acid, 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 and the resulting residue was purified by silica gel column chromatography (Wako gel C-200, eluent: ethyl acetate/n-hexane=3/7), then by preparative HPLC (YMC-ODS-5-B (3×25 cm), eluent: acetonitrile/water/ trifluoroacetic acid=90/10/0.1, flow rate: 18 mL/min), to give the desired compound (2R)-11-[3,17β-dihydroxyestra-1,3,5(10)-trien-11β-yl]-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)undecanic acid (58 mg, Yield 52%).

Workup

  1. customThe reaction mixture was quenched with 10% aqueous sodium sulfite
  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. customthe resulting residue was purified by silica gel column chromatography (Wako gel C-200, eluent: ethyl acetate/n-hexane=3/7)

Sources & evidence

ORD record
ord-a3da309c0fbb4615a6c128a93295b259
Source dataset
uspto-grants-2007_03
Patent number
US07196081B2

Reaction notes

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