3,17beta-Bis(benzyloxy)-11-(2-propenyl)estra-1,3,5(10),9(11)-tetraene → (4S,5R)-1-[(2R,9Z)-11-[3,17beta-bis(benzyloxy)estra-1,3,5(10),9(11)-tetraen-11-yl]-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)-9-undecenoyl}-3,4-dimethyl-5-phenylimidazolidin-2-one

HRID 460489Notes

Reaction equation

HRID 460489 reaction equation
C(OC1C=CC2C3[C@H]([C@H]4[C@@](CC=3CC=C)(C)[C@@H](OCC3C=CC=CC=3)CC4)CCC=2C=1)C1C=CC=CC=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.[CH2:78]([O:85][C:86]1[CH:103]=[CH:102][C:101]2[C:100]3[C@H:91]([C@H:92]4[C@@:96]([CH2:98][C:99]=3[CH2:104]/[CH:105]=[CH:106]/[CH2:107][CH2:108][CH2:109][CH2:110][CH2:111][CH2:112][C@H:113]([CH2:130][CH2:131][C:132]([F:144])([F:143])[C:133]([F:142])([F:141])[C:134]([F:140])([F:139])[C:135]([F:138])([F:137])[F:136])[C:114]([N:116]3[C@H:120]([C:121]5[CH:126]=[CH:125][CH:124]=[CH:123][CH:122]=5)[C@H:119]([CH3:127])[N:118]([CH3:128])[C:117]3=[O:129])=[O:115])([CH3:97])[C@@H:95]([O:145][CH2:146][C:147]3[CH:152]=[CH:151][CH:150]=[CH:149][CH:148]=3)[CH2:94][CH2:93]4)[CH2:90][CH2:89][C:88]=2[CH:87]=1)[C:79]1[CH:84]=[CH:83][CH:82]=[CH:81][CH:80]=1>ClCCl.C(P(C1CCCCC1)(C1CCCCC1)C1CCCCC1)(P(C1CCCCC1)(C1CCCCC1)C1CCCCC1)C1C=CC=CC=1.Cl[Ru]Cl>[CH2:78]([O:85][C:86]1[CH:103]=[CH:102][C:101]2[C:100]3[C@H:91]([C@H:92]4[C@@:96]([CH2:98][C:99]=3[CH2:104]/[CH:105]=[CH:106]\[CH2:107][CH2:108][CH2:109][CH2:110][CH2:111][CH2:112][C@H:113]([CH2:130][CH2:131][C:132]([F:143])([F:144])[C:133]([F:141])([F:142])[C:134]([F:140])([F:139])[C:135]([F:138])([F:136])[F:137])[C:114]([N:116]3[C@H:120]([C:121]5[CH:122]=[CH:123][CH:124]=[CH:125][CH:126]=5)[C@H:119]([CH3:127])[N:118]([CH3:128])[C:117]3=[O:129])=[O:115])([CH3:97])[C@@H:95]([O:145][CH2:146][C:147]3[CH:152]=[CH:151][CH:150]=[CH:149][CH:148]=3)[CH2:94][CH2:93]4)[CH2:90][CH2:89][C:88]=2[CH:87]=1)[C:79]1[CH:84]=[CH:83][CH:82]=[CH:81][CH:80]=1

Participants

6

Reactant 3

HCID 694132253,17beta-Bis(benzyloxy)-11-(2-propenyl)estra-1,3,5(10),9(11)-tetraeneHCID 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 86588541(4s,5r)-1-{(2r,9e)-11-[3,17beta-Bis(benzyloxy)estra-1,3,5(10),9(11)-tetraen-11-yl]-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)-9-undecenoyl}-3,4-dimethyl-5-phenylimidazolidin-2-one

Product 1

HCID 86588542(4S,5R)-1-[(2R,9Z)-11-[3,17beta-bis(benzyloxy)estra-1,3,5(10),9(11)-tetraen-11-yl]-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)-9-undecenoyl}-3,4-dimethyl-5-phenylimidazolidin-2-oneYield 63%

Reagents, catalysts & solvents 2

HCID 90332616Dichlororuthenium;tricyclohexyl-[phenyl-(tricyclohexyl-lambda5-phosphanyl)methyl]-lambda5-phosphaneCatalystHCID 6344DichloromethaneSolvent

Procedure

3,17β-Bis(benzyloxy)-11-(2-propenyl)estra-1,3,5(10),9(11)-tetraene (491 mg, 1.00 mmol) and the (4S,5R)-3,4-dimethyl-1-[(2R)-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)-9-decenoyl]-5-phenylimidazolidin-2-one (1.18 g, 2.00 mmol) prepared in Example 36 were dissolved in anhydrous dichloromethane (10 ml) at room temperature under nitrogen atmosphere, mixed with benzylidene-bis(tricyclohexylphosphine)-dichlororuthenium (41 mg, 0.05 mmol), and then heated under reflux followed by stirring for 6 hours under nitrogen atmosphere. After cooling, the reaction mixture was concentrated under reduced pressure and the resulting residue was purified by silica gel flash chromatography (eluent: ethyl acetate/n-hexane=3/7) to give a mixture of (4S,5R)-1-{(2R,9E)-11-[3,17β-bis(benzyloxy)estra-1,3,5(10),9(11)-tetraen-11-yl]-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)-9-undecenoyl}-3,4-dimethyl-5-phenylimidazolidin-2-one and (4S,5R)-1-{(2R,9Z)-11-[3,17β-bis(benzyloxy)estra-1,3,5(10),9(11)-tetraen-11-yl]-2-(3,3,4,4,5,5,6,6,6-nonafluorohexyl)-9-undecenoyl}-3,4-dimethyl-5-phenylimidazolidin-2-one (664 mg, Yield 63%).

Workup

  1. temperatureheated
  2. temperatureunder reflux
  3. temperatureAfter cooling
  4. concentrationthe reaction mixture was concentrated under reduced pressure
  5. customthe resulting residue was purified by silica gel flash chromatography (eluent: ethyl acetate/n-hexane=3/7)
  6. customto give

Sources & evidence

ORD record
ord-441f218a3495403b9ae8b80fdf5ba1c9
Source dataset
uspto-grants-2007_03
Patent number
US07196081B2

Reaction notes

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