Water → Cyclobutanepropanenitrile, 3,3-difluoro-β-oxo-

HRID 2409002Notes

Reaction equation

HRID 2409002 reaction equation
[H-].[Na+].[CH3:3][C:4]#[N:5].[F:6][C:7]1([F:23])[CH2:10][CH:9]([C:11](OCC2C=CC(OC)=CC=2)=[O:12])[CH2:8]1.O>O1CCOCC1>[F:6][C:7]1([F:23])[CH2:10][CH:9]([C:11](=[O:12])[CH2:3][C:4]#[N:5])[CH2:8]1

Participants

6

Reactant 4

HCID 962WaterHCID 6342AcetonitrileHCID 24758Sodium hydrideHCID 71272298HCID 71272298, compound

Product 1

HCID 72207271Cyclobutanepropanenitrile, 3,3-difluoro-β-oxo-Yield 155.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of NaH (2.85 g, 71.1 mmol) in dioxane (200 mL) was added MeCN (2.92 g. 71.1 mmol). The mixture was stirred for 20 min, then the solution of 4-methoxybenzyl 3,3-difluorocyclobutanecarboxylate (14.0 g, 54.7 mmol) in dioxane (100 mL) was added dropwise. After the mixture was heated at reflux for 4 h, the reaction mixture was poured into water (400 mL) then extracted with EtOAc (200 mL). The pH of the aqueous layer adjusted to 7 with 3N HCl and extracted with EtOAc. The organic layer was washed with brine (200 mL), dried (Na2SO4), filtered and concentrated to afford 13.5 g crude 3-(3,3-difluorocyclobutyl)-3-oxopropanenitrile which was used in the next step without purification.

Workup

  1. temperatureAfter the mixture was heated
  2. temperatureat reflux for 4 h
  3. extractionthen extracted with EtOAc (200 mL)
  4. extractionextracted with EtOAc
  5. washThe organic layer was washed with brine (200 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-e4d3be8ef6d34b1ab414f11f9acd674b
Source dataset
uspto-grants-2014_08
Patent number
US08815877B2

Reaction notes

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