Acetone → 1-(6-Fluoropyridin-3-yl)propan-2-one

Temperatur

45 °C

Anhydrous, de-gassed THF (20 mL) was added to 2-(dicyclohexylphosphino)-2′-methylbiphenyl (1.2 g, 3.2 mmol) and tris(dibenzylideneacetone)dipalladium (0) chloroform adduct (1.4 g, 1.4 mmol), and the resulting solution was warmed to 45° C. and sparged with N2. After 20 min, the reaction mixture was allowed to cool to RT, then added to a stirring, degassed mixture of 5-bromo-2-fluoropyridine (4.8 g, 27 mmol), finely ground potassium phosphate tribasic (14 g, 68 mmol), and acetone (100 mL, 1400 mmol) at RT, and the resulting mixture was sparged with N2. After 20 min, the reaction mixture was heated at reflux for 24 h, the reaction mixture was allowed to cool to room temperature, filtered through a 0.45 μm Teflon filter, and the filtrate was concentrated. The residue was purified by flash chromatography on silica gel (gradient elution; 4:1→2:1 hexane-ethyl acetate) to give 2.3 g (55%) of 1-(6-fluoropyridin-3-yl)propan-2-one as a brown oil.

1. customAnhydrous, de-gassed THF (20 mL)
2. customsparged with N2
3. temperatureto cool to RT
4. additionadded to a stirring
5. customdegassed
6. customthe resulting mixture was sparged with N2
7. waitAfter 20 min
8. temperaturethe reaction mixture was heated
9. temperatureat reflux for 24 h
10. temperatureto cool to room temperature
11. filtrationfiltered through a 0.45 μm Teflon
12. filtrationfilter
13. concentrationthe filtrate was concentrated
14. customThe residue was purified by flash chromatography on silica gel (gradient elution; 4:1→2:1 hexane-ethyl acetate)

ORD-Eintrag

ord-6de0e668e503499b8ea9c946c9e78690

Quelldatensatz

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08552181B2