Acetonitrile → 5,5,5-Trifluoro-4,4-dimethyl-3-oxopentanenitrile

HRID 1050014Notes

Reaction equation

HRID 1050014 reaction equation
[CH3:1][C:2]#[N:3].[Li]CCCC.[F:9][C:10]([F:19])([F:18])[C:11]([CH3:17])([CH3:16])[C:12](OC)=[O:13]>C1COCC1>[F:9][C:10]([F:19])([F:18])[C:11]([CH3:17])([CH3:16])[C:12](=[O:13])[CH2:1][C:2]#[N:3]

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 53485768Methyl 3,3,3-trifluoro-2,2-dimethylpropanoateHCID 178418339Butyllithium

Product 1

HCID 569543105,5,5-Trifluoro-4,4-dimethyl-3-oxopentanenitrileYield 30.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a mixture of MeCN (1.086 g, 26.5 mmol) in THF (300 mL) cooled to −78° C. was added n-BuLi (10.58 mL, 26.5 mmol). The mixture was stirred at −30° C. for 0.5 h. Then to the mixture was added methyl 3,3,3-trifluoro-2,2-dimethylpropanoate (3 g, 17.63 mmol) dropwise. The mixture was quenched with aqueous NH4Cl and extracted with DCM/MeOH (10:1, 30 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The crude material was purified by silica column chromatography (PE/EA=8:1). All fractions found to contain product by TLC (PE/EA=5:1, Rf=0.5) were combined and concentrated to yield a light yellow oil of 5,5,5-trifluoro-4,4-dimethyl-3-oxopentanenitrile (1 g, 5.30 mmol, 30% yield): 1H NMR (400 MHz, CDCl3) δ 3.79 (s, 2H), 1.41 (s, 6H).

Workup

  1. customThe mixture was quenched with aqueous NH4Cl
  2. extractionextracted with DCM/MeOH (10:1, 30 mL)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by silica column chromatography (PE/EA=8:1)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-326919cfaad34644a1930b87f771812f
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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