Tris(1,1-dimethylethyl)phosphine → HCID 17975610, compound

Temperature

70 °C

To a degassed solution of 5-fluoro-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzonitrile (5.55 g, 22.46 mmol), 2-chloro-3-fluoropyridine (2.95 g, 22.46 mmol), potassium fluoride (4.3 g, 74.14 mmol) and tris(dibenzylideneacetone)dipalladium(0) (0.824 g, 0.89 mmol) in THF (80 ml) and water (8 ml) was added tri(tert-butyl)phosphine (0.51M solution in hexane; 3.52 ml, 1.79 mmol). The reaction was heated at 70° C. for 48 h, then allowed to cool to ambient temperature. The reaction mixture was filtered through a catalyst filter, and the filtrate diluted with ethyl acetate (400 ml) and washed with water (2×100 ml). The organic phase was separated, dried (MgSO4), filtered and adsorbed onto silica gel. The crude product was chromatographed on silica, eluting with 10% ethyl acetate in isohexane, to give 5-fluoro-2-(3-fluoropyridin-2-yl)benzonitrile as a white solid (3.02 g): δH (400 MHz, CDCl3) 7.40-7.45 (2H, m), 7.51-7.61 (2H, m), 7.72-7.76 (1H, m), 8.58-8.60 (1H, m); m/z (ES+) 217.

1. temperatureto cool to ambient temperature
2. filtrationThe reaction mixture was filtered through a catalyst
3. filtrationfilter
4. additionthe filtrate diluted with ethyl acetate (400 ml)
5. washwashed with water (2×100 ml)
6. customThe organic phase was separated
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. customThe crude product was chromatographed on silica
10. washeluting with 10% ethyl acetate in isohexane

ORD record

ord-1a6bdad1287d476d9d5a785fd0ed2f25

Source dataset

uspto-grants-2007_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07226926B2