Water → 4-Chloro-3-fluoro-2-pyridinecarbonitrile

Temperature

100 °C

To a degassed solution of 2-bromo-4-chloro-3-fluoropyridine (7.3 g, 34.7 mmol) in DMF (50 mL) was added palladium tetrakistriphenylphosphine (4.01 g, 3.47 mmol) and zinc cyanide (4.07 g, 34.7 mmol) and heated to 100° C. for 20 minutes. After this time, more palladium tetrakis triphenylphosphine (4.01 g, 3.47 mmol) was added and heated to 100° C. for 90 minutes. The mixture was allowed to cool to room temperature and treated with water (200 mL) and ether (400 mL). The resulting mixture was filtered to remove insoluble solids, the filtrate was partitioned, and the aqueous layer was extracted with ether (400 mL). The combined ether extracts were washed with water (200 mL), dried (MgSO4), filtered, and the solvent removed in vacuo. This residue was purified by chromatography using silica gel column (330 g) eluting with a gradient of 10-100% CH2Cl2 in hexanes to provide the title compound. 1H NMR (CDCl3) δ=8.45 (d, 1H, J=5 Hz) and 7.65 (dd, 1H, J=5 Hz) ppm.

1. temperatureheated to 100° C. for 90 minutes
2. temperatureto cool to room temperature
3. filtrationThe resulting mixture was filtered
4. customto remove insoluble solids
5. customthe filtrate was partitioned
6. extractionthe aqueous layer was extracted with ether (400 mL)
7. washThe combined ether extracts were washed with water (200 mL)
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. customthe solvent removed in vacuo
11. customThis residue was purified by chromatography
12. washeluting with a gradient of 10-100% CH2Cl2 in hexanes

ORD record

ord-ff38527bc98d427589a4830f68a64e6a

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08404856B2