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

Temperature

-78 °C

To a mixture of acetonitrile (3.32 mL, 97 mmol) in THF (300 mL) cooled to −78° C. was added n-BuLi (56.4 mL, 141 mmol). The mixture was stirred at −30° C. for 30 min. Then to the mixture was added methyl 3,3,3-trifluoro-2,2-dimethylpropanoate (15 g, 88 mmol) dropwise. The mixture was stirred at 25° C. for 10 h. The mixture was quenched with NH4Cl (aq) and extraced with DCM/MeOH (10:1). The organic layer was dried over Na2SO4, filtered and concentrated. The crude material was purified by silica column chromatography (PE/EA=10:1). All fractions found to contain product by TLC (PE/EA=5:1, Rf=0.6) were combined and concentrated to yield a light yellow solid of 5,5,5-trifluoro-4,4-dimethyl-3-oxopentanenitrile (5 g, 27.9 mmol, 31.7% yield): 1H NMR (400 MHz, CDCl3) δ: 3.75 (s, 2H), 1.41 (s, 6H).

1. stirringThe mixture was stirred at 25° C. for 10 h
2. customThe mixture was quenched with NH4Cl (aq)
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=10:1)
7. concentrationconcentrated

ORD record

ord-3ddd9351f522471b914ddcc04789d0fc

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09035063B2