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

反応式

HRID 460485 の反応式
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]

参加物

6

反応物 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

生成物 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-one収率 57%

試薬・触媒・溶媒 2

HCID 11967259Benzylidenebis(tricyclohexylphosphine)dichlororuthenium触媒HCID 6344Dichloromethane溶媒

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-c24840afad1f4ae1bdaad34b9135a861
出典データセット
uspto-grants-2007_03
特許番号
US07196081B2

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