Iodoethane → HCID 67015674, compound

HRID 1617968Notes

Reaction equation

HRID 1617968 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[CH3:25])[CH2:9][C:10]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([CH3:18])[CH:13]=2)=[O:11])=[CH:4][CH:3]=1.[OH-:26].[K+].C(P([C:54]([CH3:57])(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.ICC.[Cl-].[NH4+]>O1CCOCC1.O.[Br-].C([N+](C)(C)C)CCCCCCCCCCCCCCC.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(OCC)(=O)C>[CH2:54]([O:26][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[CH3:25])[CH2:9][C:10]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([CH3:18])[CH:13]=2)=[O:11])=[CH:4][CH:3]=1)[CH3:57]

Participants

11

Reactant 5

HCID 6340IodoethaneHCID 14797Potassium HydroxideHCID 25517Ammonium ChlorideHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 66666695(R)-3-(4-Bromo-phenyl)-1-(2-methyl-pyridin-4-yl)-3-o-tolyl-propan-1-one

Product 1

HCID 67015674HCID 67015674, compoundYield 90%

Reagents, catalysts & solvents 5

HCID 5974Hexadecyltrimethylammonium BromideCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a white suspension of (R)-3-(4-bromo-phenyl)-1-(2-methyl-pyridin-4-yl)-3-o-tolyl-propan-1-one (example 142, step 2, 200 mg) and potassium hydroxide (171 mg) in 1,4-dioxane (1 mL) and water (2 mL) under argon were added 2-di-tert-butylphosphino-2′,4′,6′-triisopropyl-biphenyl (17.2 mg) and tris(dibenzylideneacetone)dipalladium(0) (9.3 mg). The reaction mixture was heated to 100° C. and stirred for 3 hours. After cooling at room temperature, cetyl trimethyl-ammonium bromide (18.5 mg) and iodoethane (158 mg) were added. The reaction mixture was heated to 100° C. for 1 hour. A saturated aq. solution of ammonium chloride and ethyl acetate were added, the phases were separated and the inorganic one was extracted with ethyl acetate (2×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel (0% to 50% ethyl acetate in heptane) to yield the title compound as a colourless liquid (90%), MS (ESI+): m/z=360.2 ([M+H]+).

Workup

  1. temperatureAfter cooling at room temperature
  2. temperatureThe reaction mixture was heated to 100° C. for 1 hour
  3. customthe phases were separated
  4. extractionthe inorganic one was extracted with ethyl acetate (2×)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by flash chromatography on silica gel (0% to 50% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-e2607cb74fca481a9c8d5fac64151031
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

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