Cesium carbonate → (2-Chloro-4-{[2-({2-[2-(tetrahydro-2H-pyran-2-yloxy)ethoxy]ethoxy}methyl)phenyl]amino}phenyl)(2-methylphenyl)methanone

HRID 1797302Notes

Reaction equation

HRID 1797302 reaction equation
Br[C:2]1[CH:21]=[CH:20][CH:19]=[CH:18][C:3]=1[CH2:4][O:5][CH2:6][CH2:7][O:8][CH2:9][CH2:10][O:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][O:13]1.[NH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=2[CH3:37])=[O:30])=[C:25]([Cl:38])[CH:24]=1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.CCOC(C)=O.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]>[Cl:38][C:25]1[CH:24]=[C:23]([NH:22][C:2]2[CH:21]=[CH:20][CH:19]=[CH:18][C:3]=2[CH2:4][O:5][CH2:6][CH2:7][O:8][CH2:9][CH2:10][O:11][CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][O:13]2)[CH:28]=[CH:27][C:26]=1[C:29]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[CH3:37])=[O:30]

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 99469012-(2-(2-((2-Bromobenzyl)oxy)ethoxy)ethoxy)tetrahydro-2H-pyranHCID 10988565(4-amino-2-chlorophenyl)(2-methylphenyl)Methanone

Product 1

HCID 10118970(2-Chloro-4-{[2-({2-[2-(tetrahydro-2H-pyran-2-yloxy)ethoxy]ethoxy}methyl)phenyl]amino}phenyl)(2-methylphenyl)methanone

Reagents, catalysts & solvents 4

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

Conditions

Temperature
100 °C

Procedure

Compound 420 (3.39 g, 10.3 mmol) was dissolved in 15 mL dry 1,4-dioxane in a schlenk tube under an argon atmosphere. (4-Amino-2-chlorophenyl)(2-methylphenyl)methanone (disclosed in WO 01/42189) was added and dissolved in the solvent. Rac-BINAP (0.26 g, 0.42 mmol), Pd2(dba)3 (0.19 g, 0.20 mmol) and Cs2CO3 (4.7 g, 14.4 mmol) were added, and the reaction mixture was stirred under an argon atmosphere at 100° C. for 18 h. The reaction mixture was diluted with H2O and EtOAc, and the water phase was extracted twice with EtOAc. The combined organic phases were washed with brine, dried (MgSO4) and evaporated in vacuo. The crude product was purified by flash chromatography using DCM/acetone 100:1 as the eluent to afford the title compound as an oil.

Workup

  1. dissolutiondissolved in the solvent
  2. extractionthe water phase was extracted twice with EtOAc
  3. washThe combined organic phases were washed with brine
  4. dry with materialdried (MgSO4)
  5. customevaporated in vacuo
  6. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-e5ecc4e888d04b2e8fbe7ba37f5302f0
Source dataset
uspto-grants-2006_04
Patent number
US07034015B2

Reaction notes

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