Sodium Iodide → 2-(5-Chloropyridin-3-yl)acetonitrile

Temperature

105 °C

A mixture of cyano-(2-trifluoromethyl-pyrimidin-5-yl)-acetic acid ethyl ester (240 mg, 0.93 mmol), bromomethyl cyclopropane (375 mg, 2.78 mmol) and NaI (139 mg, 0.93 mmol) in dry dioxane (2 mL) was degassed and ButOK in THF (1.11 mL, 1.11 mmol) was added at room temperature. The resulting mixture was heated to 100-110° C. for 24 h. Saturated NH4Cl solution was added to quench the reaction at 0° C. and extracted with EtOAc (5 mL×3). The organic layer was washed with brine, dried over Na2SO4 and concentrated. The crude product was purified by column chromatography on silica gel (petroleum ether/EtOAc=20:1˜5:1) to give the title compound (100 mg, yield: 44.6%). 1H NMR (CDCl3 400 MHz): δ8.94 (s, 2H), 4.09-4.01 (m, 1H), 2.05-1.95 (m, 111), 1.93-1.80 (m, 1H), 0.91-0.79 (m, 1H), 0.69-0.60 (m, 2H), 0.25-0.14 (m, 2H).

1. customwas degassed
2. customto quench
3. customthe reaction at 0° C.
4. extractionextracted with EtOAc (5 mL×3)
5. washThe organic layer was washed with brine
6. dry with materialdried over Na2SO4
7. concentrationconcentrated
8. customThe crude product was purified by column chromatography on silica gel (petroleum ether/EtOAc=20:1˜5:1)

ORD record

ord-8adee11f07a44056b9437253de297389

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09102591B2