Methyl vinyl ketone → 4,4-Bis(3-fluorophenyl)cyclohexanone

HRID 1196238Notes

Reaction equation

HRID 1196238 reaction equation
[CH3:1][C:2](=[O:5])[CH:3]=[CH2:4].[F:6][C:7]1[CH:8]=[C:9]([CH:13]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=2)[CH:14]=O)[CH:10]=[CH:11][CH:12]=1.[OH-].[K+]>C(OCC)C.C(O)C.C(OCC)(=O)C.O>[F:6][C:7]1[CH:8]=[C:9]([C:13]2([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=3)[CH2:14][CH2:1][C:2](=[O:5])[CH2:3][CH2:4]2)[CH:10]=[CH:11][CH:12]=1

Participants

8

Reactant 3

HCID 6570Methyl vinyl ketoneHCID 14797Potassium HydroxideHCID 54068354HCID 54068354, compound

Product 1

HCID 540699214,4-Bis(3-fluorophenyl)cyclohexanone

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Butenone (50.4 cc) is added to a solution of bis(3-fluorophenyl)acetaldehyde (144.5 g) in ethyl ether (500 cc), and then, after cooling to 0° C., a solution of potassium hydroxide (13.9 g) in ethanol (89 cc) is added dropwise. The reaction mixture is stirred for 2 h at 0° C. and then for 16 hours at 25° C. and diluted with ethyl acetate (300 cc) and water (500 cc). The aqueous phase is washed with ethyl acetate (300 cc). The combined organic phases are washed with a saturated sodium chloride solution (500 cc), dried over magnesium sulphate and concentrated under reduced pressure (2.7 kPa). The residue is chromatographed (in two runs) on silica gel (particle size 0.04-0.063 mm, columns 8.5 cm in diameter, 34 cm high), eluting under a nitrogen pressure of 0.5 bar with a mixture of cyclohexane and ethyl acetate (90:10). 4,4-Bis(3-fluorophenyl)cyclohexanone (90.3 g) is obtained in the form of white crystals. M.p. 95° C.

Workup

  1. waitfor 16 hours at 25° C.
  2. washThe aqueous phase is washed with ethyl acetate (300 cc)
  3. washThe combined organic phases are washed with a saturated sodium chloride solution (500 cc)
  4. dry with materialdried over magnesium sulphate
  5. concentrationconcentrated under reduced pressure (2.7 kPa)
  6. customThe residue is chromatographed (in two runs) on silica gel (particle size 0.04-0.063 mm, columns 8.5 cm in diameter, 34 cm high)
  7. washeluting under a nitrogen pressure of 0.5 bar
  8. additionwith a mixture of cyclohexane and ethyl acetate (90:10)

Sources & evidence

ORD record
ord-29a27ec653b24289bc57c5c049140f12
Source dataset
uspto-grants-1992_05
Patent number
US05112988

Reaction notes

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