3-Methoxy-7alpha-(2-propenyl)estra-1,3,5(10)-trien-17beta-ol → (4S,5R)-3,4-dimethyl-1-[(2R,9Z)-11-(17beta-hydroxy-3-methoxyestra-1,3,5(10)-trien-7alpha-yl)-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)-9-undecenoyl]-5-phenylimidazolidin-2-one

HRID 460485

Reaction equation

HRID 460485 reaction equation
COC1C=CC2[C@@H]3[C@H]([C@H]4[C@@](CC3)(C)[C@@H](O)CC4)[C@H](CC=C)CC=2C=1.CN1[C@@H](C)[C@@H](C2C=CC=CC=2)N(C(=O)[C@@H](CCC(F)(F)C(F)(F)C(F)(F)C(F)(F)F)CCCCCCC=C)C1=O.[CH3:65][N:66]1[C@@H:70]([CH3:71])[C@@H:69]([C:72]2[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=2)[N:68]([C:78](=[O:125])[C@@H:79]([CH2:110][CH2:111][C:112]([F:124])([F:123])[C:113]([F:122])([F:121])[C:114]([F:120])([F:119])[C:115]([F:118])([F:117])[F:116])[CH2:80][CH2:81][CH2:82][CH2:83][CH2:84][CH2:85]/[CH:86]=[CH:87]/[CH2:88][C@@H:89]2[CH2:106][C:105]3[CH:104]=[C:103]([O:107][CH3:108])[CH:102]=[CH:101][C:100]=3[C@@H:99]3[C@@H:90]2[C@H:91]2[C@@:95]([CH2:97][CH2:98]3)([CH3:96])[C@@H:94]([OH:109])[CH2:93][CH2:92]2)[C:67]1=[O:126]>ClCCl.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1C=CC(C=[Ru](Cl)Cl)=CC=1>[CH3:65][N:66]1[C@@H:70]([CH3:71])[C@@H:69]([C:72]2[CH:73]=[CH:74][CH:75]=[CH:76][CH:77]=2)[N:68]([C:78](=[O:125])[C@@H:79]([CH2:110][CH2:111][C:112]([F:123])([F:124])[C:113]([F:122])([F:121])[C:114]([F:120])([F:119])[C:115]([F:118])([F:117])[F:116])[CH2:80][CH2:81][CH2:82][CH2:83][CH2:84][CH2:85]/[CH:86]=[CH:87]\[CH2:88][C@@H:89]2[CH2:106][C:105]3[CH:104]=[C:103]([O:107][CH3:108])[CH:102]=[CH:101][C:100]=3[C@@H:99]3[C@@H:90]2[C@H:91]2[C@@:95]([CH2:97][CH2:98]3)([CH3:96])[C@@H:94]([OH:109])[CH2:93][CH2:92]2)[C:67]1=[O:126]

Participants

6

Reactant 3

HCID 694148073-Methoxy-7alpha-(2-propenyl)estra-1,3,5(10)-trien-17beta-olHCID 86588536(4S,5R)-3,4-dimethyl-1-[(2R)-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)-9-decenoyl]-5-phenylimidazolidin-2-oneHCID 86588683(4S,5R)-3,4-dimethyl-1-[(2R,9E)-11-(17beta-hydroxy-3-methoxyestra-1,3,5(10)-trien-7alpha-yl)-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)-9-undecenoyl]-5-phenylimidazolidin-2-one

Product 1

HCID 86600466(4S,5R)-3,4-dimethyl-1-[(2R,9Z)-11-(17beta-hydroxy-3-methoxyestra-1,3,5(10)-trien-7alpha-yl)-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)-9-undecenoyl]-5-phenylimidazolidin-2-oneYield 57%

Reagents, catalysts & solvents 2

HCID 11967259Benzylidenebis(tricyclohexylphosphine)dichlororutheniumCatalystHCID 6344DichloromethaneSolvent

Procedure

3-Methoxy-7α-(2-propenyl)estra-1,3,5(10)-trien-17β-ol (377 mg, 1.16 mmol) and (4S,5R)-3,4-dimethyl-1-[(2R)-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)-9-decenoyl]-5-phenylimidazolidin-2-one (1.36 g, 2.31 mmol) were dissolved in anhydrous dichloromethane (12 ml) at room temperature under nitrogen atmosphere. To this solution, benzylidene-bis(tricyclohexylphosphine)dichlororuthenium (47.5 mg, 5.78×10−2 mmol) was added, and the resulting mixture was heated under reflux for 5 hours under nitrogen atmosphere. After cooling, the reaction mixture was filtered through an alumina pad. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel flash chromatography (Kanto Kagaku, silica gel 60 (spherical, neutral), 40–100 μm, eluent: ethyl acetate/n-hexane=1/1) to give a mixture of (4S,5R)-3,4-dimethyl-1-[(2R,9E)-11-(17β-hydroxy-3-methoxyestra-1,3,5(10)-trien-7α-yl)-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)-9-undecenoyl]-5-phenylimidazolidin-2-one and (4S,5R)-3,4-dimethyl-1-[(2R,9Z)-11-(17β-hydroxy-3-methoxyestra-1,3,5(10)-trien-7α-yl)-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)-9-undecenoyl]-5-phenylimidazolidin-2-one (579 mg, Yield 57%).

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureunder reflux for 5 hours under nitrogen atmosphere
  3. temperatureAfter cooling
  4. filtrationthe reaction mixture was filtered through an alumina pad
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe resulting residue was purified by silica gel flash chromatography (Kanto Kagaku, silica gel 60 (spherical, neutral), 40–100 μm, eluent: ethyl acetate/n-hexane=1/1)
  7. customto give

Sources & evidence

ORD record
ord-c24840afad1f4ae1bdaad34b9135a861
Source dataset
uspto-grants-2007_03
Patent number
US07196081B2

Linked notes

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