Reaktion #612522

Reaktionsgleichung

(S)-5,5-dimethyl-4-phenyloxazolidin-2-one

2-fluoro-5-iodopyridine

N,N′-dimethylethylenediamine

potassium phosphate

→

(S)-3-(6-fluoropyridin-3-yl)-5,5-dimethyl-4-phenyloxazolidin-2-one

Ausbeute 72.6%

Lösungsmittel

water

dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe vessel was purged with nitrogen
2. 2
   TemperaturThe vessel was heated
3. 3
   Temperaturto reflux overnight
4. 4
   Sonstigeproviding an orange suspension
5. 5
   Filtrationthe resulting slurry was filtered through Celite® brand
6. 6
   Filtrationfilter aid
7. 7
   SonstigeThe yellow filtrate was transferred to a separatory funnel
8. 8
   workup.ADDITIONdiluted with water
9. 9
   Extraktionextracted with EtOAc (2×)
10. 10
    TrocknenThe combined organic layers were dried with Na2SO4
11. 11
    Filtrationfiltered
12. 12
    Sonstigedried under reduced pressure
13. 13
    SonstigeThe residue was purified with a 50 g SNAP column (Biotage)

Vorschrift

To a round bottom flask were added (S)-5,5-dimethyl-4-phenyloxazolidin-2-one (commercially available from Sigma-Aldrich, Milwaukee, Wis.) (0.750 g, 3.92 mmol), 2-fluoro-5-iodopyridine (commercially available from Sigma-Aldrich, Milwaukee, Wis.) (1.749 g, 7.84 mmol), and dioxane (15.69 mL). Tribasic potassium phosphate (4.16 g, 19.61 mmol) was then added to the mixture. The vessel was purged with nitrogen followed by the addition of N,N′-dimethylethylenediamine (0.844 mL, 7.84 mmol) and copper (I) iodide (0.747 g, 3.92 mmol). The vessel was heated to reflux overnight providing an orange suspension. To the mixture was added water (˜10 mL), and the resulting slurry was filtered through Celite® brand filter aid. The yellow filtrate was transferred to a separatory funnel, diluted with water and extracted with EtOAc (2×). The combined organic layers were dried with Na2SO4, filtered, and dried under reduced pressure. The residue was purified with a 50 g SNAP column (Biotage) ramping EtOAc in heptane (0-35%, then isocratic at 35%) to elute (S)-3-(6-fluoropyridin-3-yl)-5,5-dimethyl-4-phenyloxazolidin-2-one (0.815 g, 2.85 mmol, 72.6% yield) which was obtained as a white solid upon drying. 1H NMR (400 MHz, CDCl3) δ=8.21 (ddd, J=3.0, 6.8, 9.0 Hz, 1H), 8.02-7.99 (m, 1H), 7.41-7.34 (m, 3H), 7.20-7.16 (m, 2H), 6.88 (ddd, J=0.6, 3.5, 8.9 Hz, 1H), 5.00 (s, 1H), 1.71 (s, 3H), 1.04 (s, 3H). m/z (ESI) 287.1 (M+H)+.

Quelle