Reaktion #721723

Reaktionsgleichung

6-chloro-2-iodopyridin-3-amine

isopropylmagnesium chloride

2-bromo-3-fluoropyridine

→

6-chloro-3′-fluoro-[2,2′-bipyridin]-3-amine

Ausbeute 69.0%

Lösungsmittel

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeA 3-neck 1000 mL RBF was dried under vacuum
2. 2
   Temperaturcooled with a water bath
3. 3
   Sonstigedid not exceed 30° C
4. 4
   workup.STIRRINGstirred at room temperature overnight
5. 5
   Temperaturheated
6. 6
   Temperaturat reflux overnight
7. 7
   TemperaturAfter cooled to room temperature
8. 8
   Sonstigethe reaction was quenched with sat. aq. NaHCO3 and water
9. 9
   FiltrationThe precipitate was filtered out
10. 10
    Waschenwashed with EtOAc
11. 11
    ExtraktionThe filtrate was extracted with EtOAc
12. 12
    SonstigeThe crude product was purified by column chromatography in 40-50% EtOAc/hexanes with column

Vorschrift

A 3-neck 1000 mL RBF was dried under vacuum, then charged with isopropylmagnesium chloride (78 mL, 156 mmol) and cooled with a water bath. 2-bromo-3-fluoropyridine (14.37 mL, 142 mmol) was added dropwise making sure temperature did not exceed 30° C. The reaction was stirred at room temperature overnight, then treated dropwise with zinc(II) chloride (341 mL, 170 mmol) over 3 hrs and stirred at room temperature overnight. This suspension was then added dropwise via canula to a degassed, 65° C. solution of Pd(PPh3)4 (8.21 g, 7.10 mmol) and 6-chloro-2-iodopyridin-3-amine (39.8 g, 156 mmol) in tetrahydrofuran (THF) (Volume: 474 mL) and heated at reflux overnight. After cooled to room temperature, the reaction was quenched with sat. aq. NaHCO3 and water. The precipitate was filtered out and washed with EtOAc. The filtrate was extracted with EtOAc. The crude product was purified by column chromatography in 40-50% EtOAc/hexanes with column conditioned in 20% TEA/hexanes to give 6-chloro-3′-fluoro-[2,2′-bipyridin]-3-amine (21.8 g, 69% yield).

Quelle