Cesium carbonate → (5R)-5-[(E)-2-{5-[(1E)-4-{[tert-butyl(dimethyl)silyl]oxy}but-1-en-1-yl]-6-methoxypyridin-2-yl}-2-(4-tert-butylphenyl)ethenyl]-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one

HRID 70661Notes

Reaction equation

HRID 70661 reaction equation
[O:1]([CH2:9][CH2:10]/[CH:11]=[CH:12]/B1OC(C)(C)C(C)(C)O1)[Si:2]([C:5]([CH3:8])([CH3:7])[CH3:6])([CH3:4])[CH3:3].O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:45]1[CH:46]=[CH:47][C:48](/[C:53](/[C:72]2[CH:77]=[CH:76][C:75]([C:78]([CH3:81])([CH3:80])[CH3:79])=[CH:74][CH:73]=2)=[CH:54]/[C@@H:55]2[N:59]([CH2:60][C:61]3[CH:66]=[CH:65][C:64]([O:67][CH3:68])=[CH:63][C:62]=3[O:69][CH3:70])[C:58](=[O:71])[CH2:57][CH2:56]2)=[N:49][C:50]=1[O:51][CH3:52]>O1CCOCC1.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[Si:2]([O:1][CH2:9][CH2:10]/[CH:11]=[CH:12]/[C:45]1[CH:46]=[CH:47][C:48](/[C:53](/[C:72]2[CH:73]=[CH:74][C:75]([C:78]([CH3:81])([CH3:80])[CH3:79])=[CH:76][CH:77]=2)=[CH:54]/[C@@H:55]2[N:59]([CH2:60][C:61]3[CH:66]=[CH:65][C:64]([O:67][CH3:68])=[CH:63][C:62]=3[O:69][CH3:70])[C:58](=[O:71])[CH2:57][CH2:56]2)=[N:49][C:50]=1[O:51][CH3:52])([C:5]([CH3:6])([CH3:7])[CH3:8])([CH3:3])[CH3:4]

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 521585Tris(furan-2-yl)phosphaneHCID 16217344(E)-tert-Butyldimethyl((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-en-1-yl)oxy)silaneHCID 67397955(5R)-5-[(E)-2-(5-bromo-6-methoxypyridin-2-yl)-2-(4-tert-butylphenyl)ethenyl]-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one

Product 1

HCID 67397853(5R)-5-[(E)-2-{5-[(1E)-4-{[tert-butyl(dimethyl)silyl]oxy}but-1-en-1-yl]-6-methoxypyridin-2-yl}-2-(4-tert-butylphenyl)ethenyl]-1-(2,4-dimethoxybenzyl)pyrrolidin-2-oneYield 100%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
65 °C

Procedure

trans-4-(tert-Butyldimethylsiloxy)-1-buten-1-ylboronic acid pinacol ester (296 mg), tris(dibenzylideneacetone)dipalladium(0) (48 mg), tri(2-furyl)phosphine (73 mg) and cesium carbonate (354 mg) were added to a solution of (5R)-5-[(E)-2-(5-bromo-6-methoxypyridin-2-yl)-2-(4-tert-butylphenyl)ethenyl]-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one obtained in Reference Example 4-42(1) (300 mg) in 1,4-dioxane (3 mL)-water (1 mL), and the mixture was stirred at an external temperature of 65° C. for three hours. The reaction solution was left to cool, diluted with ethyl acetate and filtered through celite. The filtrate was washed with brine and dried over sodium sulfate. After filtration, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1→3:2) to give (5R)-5-[(E)-2-{5-[(1E)-4-{[tert-butyl(dimethyl)silyl]oxy}but-1-en-1-yl]-6-methoxypyridin-2-yl}-2-(4-tert-butylphenyl)ethenyl]-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one as a yellow oil (399 mg, 100%).

Workup

  1. waitThe reaction solution was left
  2. temperatureto cool
  3. filtrationfiltered through celite
  4. washThe filtrate was washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationAfter filtration
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1→3:2)

Sources & evidence

ORD record
ord-f7372ae500a747bfb5f028d332c9a370
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Reaction notes

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