2-Bromo-3-fluoropyridine → HCID 117814864, compound

Participants

Reaction Steps

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).

Provenance & Evidence