Dimethylformamide → 5-[(2,2,2-Trifluoroethoxy)methyl]pyridine-2-carbonitrile

2-Chloro-5-[(2,2,2-trifluoroethoxy)methyl]pyridine (Intermediate 227, 0.537 g, 2.38 mmol) was dissolved in DMF (6 mL) and zinc cyanide (0.279 g, 2.38 mmol) was added. The mixture was degassed by stirring under a flow of nitrogen for 10 min. Tetrakis(triphenylphosphine)palladium(0) (0.275 g, 0.24 mmol) and further DMF (2 mL) were added and the mixture heated to 100 C in a sealed tube for 6 h. The mixture was partitioned between EtOAc (50 mL) and water (50 mL) and the organic layer washed with further water (2×50 mL). The organic layer was dried over sodium sulfate and concentrated to yield an orange oil. This was purified by FCC, eluting with a gradient of 0-30% EtOAc in heptane to afford the title compound as a colourless oil (0.255 g, 50%). 1H NMR (500 MHZ, CDCl3) δ ppm 8.62 (1H, d), 7.79 (1H, dd), 7.66 (1H, d), 4.72 (2H, s) and 3.89 (2H, q).

1. customThe mixture was degassed
2. temperaturethe mixture heated to 100 C in a sealed tube for 6 h
3. customThe mixture was partitioned between EtOAc (50 mL) and water (50 mL)
4. washthe organic layer washed with further water (2×50 mL)
5. dry with materialThe organic layer was dried over sodium sulfate
6. concentrationconcentrated
7. customto yield an orange oil
8. customThis was purified by FCC
9. washeluting with a gradient of 0-30% EtOAc in heptane

ORD record

ord-4a0bb422b20442bf94ab36907c5ba802

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08895733B2