Hydrochloric Acid → 4,4-Difluoro-1-cyclohexyl-1,3-butanedione

HRID 1860580Notes

Reaction equation

HRID 1860580 reaction equation
[CH:1]1([C:7]([CH3:9])=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[F:10][CH:11]([F:17])[C:12](OCC)=[O:13].C[O-].[Na+].Cl>COCCOC.O.CCOC(C)=O>[F:10][CH:11]([F:17])[C:12](=[O:13])[CH2:9][C:7]([CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)=[O:8]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 9961Ethyl difluoroacetateHCID 13207Cyclohexyl methyl ketoneHCID 10942334Sodium Methoxide

Product 1

HCID 230055004,4-Difluoro-1-cyclohexyl-1,3-butanedione

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of cyclohexylmethylketone (2.52 g, 20 mmol) in DME (50 mL) at −20° C. was added ethyl difluoroacetate (7.44 g, 60 mmol) and sodium methoxide (6.48 g, 120 mmol), and the resulting reaction mixture was then stirred at room temperature for 1 hour. EtOAc (500 ml) and water (50 ml) were added, and the pH of the aqueous layer was adjusted to 6 by addition of 1 N HCl solution. The organic layer was washed with brine (50 ml), dried over Na2SO4, and concentrated in vacuo to give the title (3.8 g, 93%). This was used for the next coupling step without further purification.

Workup

  1. customthe resulting reaction mixture
  2. washThe organic layer was washed with brine (50 ml)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customto give the title (3.8 g, 93%)
  6. customThis was used for the next coupling step without further purification

Sources & evidence

ORD record
ord-387293def15542ec96b3ad62030be607
Source dataset
uspto-grants-2003_03
Patent number
US06531492B1

Reaction notes

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