Cesium fluoride → [2-chloro-4-({2-[(1E)-3-hydroxyprop-1-enyl]phenyl}amino)phenyl](2-methylphenyl)methanone

HRID 1797299Notes

Reaction equation

HRID 1797299 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2Br)[CH:5]=[CH:4][C:3]=1[C:16]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[CH3:24])=[O:17].[F-].[Cs+].C([Sn](CCCC)(CCCC)/[CH:32]=[CH:33]/[CH2:34][OH:35])CCC>O1CCOCC1.C(#N)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]>[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2/[CH:32]=[CH:33]/[CH2:34][OH:35])[CH:5]=[CH:4][C:3]=1[C:16]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[CH3:24])=[O:17]

Participants

7

Reactant 3

HCID 25953Cesium fluorideHCID 10043273(E)-3-(tributylstannyl)prop-2-en-1-olHCID 10157841{2-Chloro-4-[(2-bromophenyl)amino]phenyl}(2-methylphenyl)methanone

Product 1

HCID 10199625[2-chloro-4-({2-[(1E)-3-hydroxyprop-1-enyl]phenyl}amino)phenyl](2-methylphenyl)methanone

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6342AcetonitrileSolventHCID 312751,4-DioxaneSolvent2×

Procedure

Under an atmosphere of argon, a solution of {2-chloro-4-[(2-bromophenyl)amino]phenyl}(2-methylphenyl)methanone (300 mg) (disclosed in WO 01/42189) in dioxane (1.5 mL) and a solution of P-t-Bu3 (18 mg) in dioxane (1.0 mL) were added in turn to a Schlenk tube charged with Pd2(dba)3 (21 mg) and CsF (152 mg). (2E)-3-(tributylstannyl)prop-2-en-1-ol (273 mg) was then added by syringe, and the Schlenk tube was sealed, placed in an 35–50° C. oil bath, and stirred for 48 h. The reaction mixture was then cooled to room temperature, diluted with acetonitrile, and filtered through a pad of celite. The celite was washed with acetonitrile, and the combined organic phase was then washed thoroughly with petroleum ether and concentrated in vacuo. The product was purified by flash chromatography eluting with a mixture of petroleum ether/EtOAc 4:1 to afford the title compound as a yellow syrup.

Workup

  1. customthe Schlenk tube was sealed
  2. customplaced in an 35–50° C.
  3. filtrationfiltered through a pad of celite
  4. washThe celite was washed with acetonitrile
  5. washthe combined organic phase was then washed thoroughly with petroleum ether
  6. concentrationconcentrated in vacuo
  7. customThe product was purified by flash chromatography
  8. washeluting with a mixture of petroleum ether/EtOAc 4:1

Sources & evidence

ORD record
ord-d74b809b38c2407b8e725e1e49d4f819
Source dataset
uspto-grants-2006_04
Patent number
US07034015B2

Reaction notes

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