Ethyl 4-bromobenzoate → HCID 117840693, compound

HRID 1520296Notes

Reaction equation

HRID 1520296 reaction equation
[F:1][C:2]([F:20])([F:19])[CH2:3][CH2:4][CH:5]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:9][N:8]=1)[NH2:6].Br[C:22]1[CH:32]=[CH:31][C:25]([C:26]([O:28][CH2:29][CH3:30])=[O:27])=[CH:24][CH:23]=1.C(P(C(C)(C)C)C1N(C2C(C3C=CC=CC=3)=NN(C3C=CC=CC=3)C=2C2C=CC=CC=2)N=CC=1)(C)(C)C.CC(C)([O-])C.[Na+]>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.C(O)(C)(C)C>[F:20][C:2]([F:1])([F:19])[CH2:3][CH2:4][CH:5]([NH:6][C:22]1[CH:32]=[CH:31][C:25]([C:26]([O:28][CH2:29][CH3:30])=[O:27])=[CH:24][CH:23]=1)[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:9][N:8]=1

Participants

8

Reactant 4

HCID 22043Ethyl 4-bromobenzoateHCID 11547931BippyPhosHCID 23676156Sodium t-butoxideHCID 117840145HCID 117840145, compound

Product 1

HCID 117840693HCID 117840693, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent2×HCID 6386tert-ButanolSolvent

Conditions

Temperature
70 °C

Procedure

Under a nitrogen atmosphere, a mixture of 4,4,4-trifluoro-1-(5-phenylpyridin-2-yl)butan-1-amine (125.1 mg) obtained in step E, ethyl 4-bromobenzoate (0.214 mL), tris(dibenzylideneacetone)dipalladium (82 mg), 5-(di-tert-butylphosphino)-1′,3′,5′-triphenyl-1′H-[1,4′]bipyrazole (90 mg), sodium tert-butoxide (129 mg), tert-butanol (2.008 mL) and water (0.223 mL) was stirred at 70° C. overnight. To the reaction mixture was added water at room temperature, and the insoluble material was filtered off through celite. The filtrate was extracted with ethyl acetate, and the extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was fractionated by HPLC(C18, mobile phase: water/acetonitrile (10 mM ammonium hydrogencarbonate-containing system)). The solvent was evaporated under reduced pressure, and the residue was extracted with ethyl acetate. The extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to give the title compound (35.3 mg).

Workup

  1. filtrationthe insoluble material was filtered off through celite
  2. extractionThe filtrate was extracted with ethyl acetate
  3. washthe extract was washed with water and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customThe solvent was evaporated under reduced pressure
  7. extractionthe residue was extracted with ethyl acetate
  8. washThe extract was washed with water and saturated brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-5eb160c3375349f3b2b54218448b5a67
Source dataset
uspto-grants-2015_07
Patent number
US09073864B2

Reaction notes

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