Cyclohexyl methyl ketone → 1-Cyclohexyl-2-(4-cyclohexyloxy-phenyl)-ethanone

HRID 1971986Notes

Reaction equation

HRID 1971986 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:4][CH:3]=1.[CH:15]1([C:21]([CH3:23])=[O:22])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]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.CC(C)([O-])C.[K+]>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]>[CH:15]1([C:21](=[O:22])[CH2:23][C:2]2[CH:7]=[CH:6][C:5]([O:8][CH:9]3[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]3)=[CH:4][CH:3]=2)[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1

Participants

6

Reactant 4

HCID 13207Cyclohexyl methyl ketoneHCID 634876Binap, (A+-)-HCID 111397141-Bromo-4-(cyclohexyloxy)benzeneHCID 23665647Potassium tert-butoxide

Product 1

HCID 673746771-Cyclohexyl-2-(4-cyclohexyloxy-phenyl)-ethanoneYield 29.7%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
90 °C

Procedure

A stirred suspension of 1-bromo-4-cyclohexyloxy-benzene (3.92 mmol, 1.0 g), cyclohexylmethylketone (5.92 mmol, 0.83 mL), (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (1.88 mmol, 1.17 g), tris(dibenzylideneacetone)dipalladium(0) (0.78 mmol, 0.72 g), and potassium t-butoxide (7.84 mmol, 0.88 g) were heated to 90° C. for 12 h in a sealed vial. The reaction was cooled and partitioned in water (50 mL) and diethyl ether (50 mL). The mixture was filtered through fluted filter paper and the layers were separated. The aqueous layer was washed with diethyl ether (3×20 mL). The combined organic layers were washed with brine (10 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified on a 24 g SiO2 cartridge using an ethyl acetate/hexanes gradient to give 1-cyclohexyl-2-(4-cyclohexyloxy-phenyl)-ethanone (0.35 g).

Workup

  1. temperatureThe reaction was cooled
  2. custompartitioned in water (50 mL)
  3. filtrationThe mixture was filtered
  4. filtrationthrough fluted filter paper
  5. customthe layers were separated
  6. washThe aqueous layer was washed with diethyl ether (3×20 mL)
  7. washThe combined organic layers were washed with brine (10 mL)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe crude product was purified on a 24 g SiO2 cartridge

Sources & evidence

ORD record
ord-16554b9ba629469aa92166598cadd8b2
Source dataset
uspto-grants-2013_04
Patent number
US08431575B2

Reaction notes

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