反应详情

温度

140 °C

A solution of 2-[2-chloro-6-(trifluoromethyl)pyridin-4-yl]propan-2-ol (0.230 g, 0.960 mmol, from Step B) and zinc cyanide (0.676 g, 5.76 mmol) in N-methylpyrrolidinone (4 mL) was degassed by bubbling a stream of nitrogen through the solution for 10 minutes. Tetrakis(triphenylphosphine)palladium(0) (0.22 g, 0.19 mmol) was added and degassed similarly for 5 additional minutes. The vial was sealed and heated in the microwave to 140° C. for 10 minutes. The reaction mixture was worked up by partitioning between water and ethyl acetate, extracting (3×), and drying the combined extracts over sodium sulfate. The dried extract was then filtered and concentrated. Flash chromatography on silica gel, eluting with a gradient from 0-25% EtOAc/Hexanes afforded product (110 mg, 50%). 1H NMR (400 MHz, CDCl3) δ 8.00 (d, J=1.5 Hz, 1H), 7.99 (d, J=1.6 Hz, 1H), 1.62 (s, 6H); 19F NMR (282 MHz, CDCl3) δ−68.39 (s); LCMS (M+H)+: 231.1.

1. customby bubbling a stream of nitrogen through the solution for 10 minutes
2. customdegassed similarly for 5 additional minutes
3. customThe vial was sealed
4. customby partitioning between water and ethyl acetate
5. extractionextracting (3×)
6. dry with materialdrying the combined extracts over sodium sulfate
7. extractionThe dried extract
8. filtrationwas then filtered
9. concentrationconcentrated
10. washFlash chromatography on silica gel, eluting with a gradient from 0-25% EtOAc/Hexanes afforded product (110 mg, 50%)