Cesium carbonate → Tert-butyl 2-(2-(benzyloxy)-5-(4-(tert-butyldimethylsilyloxy)piperidin-1-yl)benzamido)-4-phenylbenzoate

HRID 454597Notes

Reaction equation

HRID 454597 reaction equation
[Si:1]([O:8][CH:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[CH2:55]([O:62][C:63]1[CH:90]=[CH:89][C:88](Br)=[CH:87][C:64]=1[C:65]([NH:67][C:68]1[CH:80]=[C:79]([C:81]2[CH:86]=[CH:85][CH:84]=[CH:83][CH:82]=2)[CH:78]=[CH:77][C:69]=1[C:70]([O:72][C:73]([CH3:76])([CH3:75])[CH3:74])=[O:71])=[O:66])[C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.O.C1(C)C=CC=CC=1>[CH2:55]([O:62][C:63]1[CH:90]=[CH:89][C:88]([N:12]2[CH2:11][CH2:10][CH:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH2:14][CH2:13]2)=[CH:87][C:64]=1[C:65]([NH:67][C:68]1[CH:80]=[C:79]([C:81]2[CH:86]=[CH:85][CH:84]=[CH:83][CH:82]=2)[CH:78]=[CH:77][C:69]=1[C:70]([O:72][C:73]([CH3:76])([CH3:75])[CH3:74])=[O:71])=[O:66])[C:56]1[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=1

Participants

10

Reactant 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 114813284-((Tert-butyldimethylsilyl)oxy)piperidineHCID 66990333Tert-butyl 2-(2-(benzyloxy)-5-bromobenzamido)-4-phenylbenzoate

Product 1

HCID 66991386Tert-butyl 2-(2-(benzyloxy)-5-(4-(tert-butyldimethylsilyloxy)piperidin-1-yl)benzamido)-4-phenylbenzoateYield 86%

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-(Tert-butyldimethylsilyloxy)piperidine (0.23 g), cesium carbonate (0.44 g), tris(dibenzylideneacetone)dipalladium(0) (9.8 mg), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (26 mg), and palladium(II) acetate (4.8 mg) were added to a toluene (4.5 mL) solution of tert-butyl 2-(2-(benzyloxy)-5-bromobenzamido)-4-phenylbenzoate (0.30 g), followed by heating to reflux under a nitrogen atmosphere for 4 hours and 30 minutes. The reaction mixture was cooled to room temperature, and water and ethyl acetate were added thereto. The insoluble substance was removed by filtration. The organic layer was separated, washed with saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [Kanto Chemical Co., Inc., silica gel 60 (spherical), eluent: 100-90% hexane/ethyl acetate] to obtain 0.32 g of tert-butyl 2-(2-(benzyloxy)-5-(4-(tert-butyldimethylsilyloxy)piperidin-1-yl)benzamido)-4-phenylbenzoate.

Workup

  1. temperatureby heating
  2. temperatureto reflux under a nitrogen atmosphere for 4 hours and 30 minutes
  3. customThe insoluble substance was removed by filtration
  4. customThe organic layer was separated
  5. washwashed with saturated aqueous solution of sodium chloride
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customthe solvent was evaporated under reduced pressure
  8. customThe obtained residue was purified by silica gel column chromatography [Kanto Chemical Co., Inc., silica gel 60 (spherical), eluent: 100-90% hexane/ethyl acetate]

Sources & evidence

ORD record
ord-fb85de4f79ae4305a858683803eb8c04
Source dataset
uspto-grants-2013_07
Patent number
US08492582B2

Reaction notes

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