Dimethylformamide → 3-Fluoro-4-methylpyridine-2-carbonitrile

Temperatur

90 °C

To a mixture of 2-bromo-3-fluoro-4-methylpyridine (4.89 g, 25.7 mmol) and zinc cyanide (3.02 g, 25.7 mmol) in DMF (45 mL) was added palladium tetra(triphenylphosphine) (2.97 g, 2.57 mmol). The mixture was degassed and then heated to 90° C. for 18 hours. After this time, the mixture was diluted with water (500 mL) and EtOAc (500 mL), filtered and the resulting layers were separated. The aqueous layer was further extracted with EtOAc (2×500 mL). The combined extracts were washed with water (300 mL), dried over MgSO4, filtered and the solvent removed in vacuo. The resulting residue was chromatographed using RediSep column (330 g) and eluting with a gradient of 0-100% EtOAc/CH2Cl2. The pure fractions were combined and the solvent removed in vacuo to give title compound.

1. customThe mixture was degassed
2. additionAfter this time, the mixture was diluted with water (500 mL) and EtOAc (500 mL)
3. filtrationfiltered
4. customthe resulting layers were separated
5. extractionThe aqueous layer was further extracted with EtOAc (2×500 mL)
6. washThe combined extracts were washed with water (300 mL)
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. customthe solvent removed in vacuo
10. customThe resulting residue was chromatographed
11. washeluting with a gradient of 0-100% EtOAc/CH2Cl2
12. customthe solvent removed in vacuo

ORD-Eintrag

ord-fb47779414de475193bd8e3ba99254f1

Quelldatensatz

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08404856B2