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

반응식

HRID 460485 반응식
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]

참가 물질

6

반응물 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

생성물 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-one수율 57%

시약·촉매·용매 2

HCID 11967259Benzylidenebis(tricyclohexylphosphine)dichlororuthenium촉매HCID 6344Dichloromethane용매

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-c24840afad1f4ae1bdaad34b9135a861
출처 데이터셋
uspto-grants-2007_03
특허 번호
US07196081B2

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