Dimethylformamide → 2-Fluoro-5-methoxypyridine

Temperature

45 °C

To a 20 mL microwave vial, 6-fluoropyridin-3-ol (Alfa Aesar, 1.04 g, 9.18 mmol), potassium carbonate (1.90 g, 13.8 mmol) and methyl iodide (Aldrich, 0.689 mL, 11.0 mmol) were mixed into DMF (6 mL). The brown mixture was stirred at 45° C. for 2.5 h. The mixture was diluted with water and the aqueous phase was extracted with EtOAc (3×20 mL). The combined organic phases were washed with saturated aqueous sodium chloride (30 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo to afford 2-fluoro-5-methoxypyridine (1.08 g, 92% yield) as a light brown oil. This material was used in the next reaction without further purification. 1H NMR (400 MHz, CDCl3) δ ppm 7.79-7.85 (m, 1H) 7.33 (td, J=6.02, 3.23 Hz, 1H) 6.86 (dd, J=8.90, 3.42 Hz, 1H) 3.85 (s, 3H). m/z (ESI, positive ion): 128.1 (M+H)+.

1. extractionthe aqueous phase was extracted with EtOAc (3×20 mL)
2. washThe combined organic phases were washed with saturated aqueous sodium chloride (30 mL)
3. dry with materialThe organic phase was dried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo

ORD record

ord-15210ee99a9f480985bebeb743f151a0

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08772480B2