Sodium Iodide → HCID 178517851, compound

Participants

Reaction Conditions

Reaction Steps

To 3,6-difluoro-2-methoxypyridine (21.5 g, 148 mmol) in acetonitrile (250 ml) was added sodium iodide (66.6 g, 445 mmol) and chlorotrimethylsilane (56.8 ml, 445 mmol). The resulting mixture was heated at 80-85° C. for 2.5 hr. The mixture was cooled to ambient temperature and diluted with EtOAc (300 mL) and water (300 mL) and vigorously stirred for another hr. The layers were separated, and the aqueous phase was extracted with additional ethyl acetate (200 mL). The combined organic layers were washed sequentially with 0.6 N aqueous HCl (250 mL) and brine (250 mL) and concentrated in vacuo to yield a slurry. The slurry was filtered and rinsed three times with cold acetonitrile to yield 10.8 g of desired product as a white solid. The filtrate was concentrated and purified by flash chromatography over silica gel (heptanes:ethyl acetate gradient) to give an additional 4.2 g (77% yield combined) of 3,6-difluoro-2-hydroxypyridine as a white solid. LCMS (m/z): 132.0 [M+H]+; retention time=0.47 min.

Provenance & Evidence