Dimethylformamide → 2-Fluoro-5-(2-methoxyethoxy)pyridine

Participants

Reaction Conditions

Reaction Steps

To a 20 mL microwave vial, 6-fluoropyridin-3-ol (Alfa Aesar, 1.04 g, 9.24 mmol), 2-bromoethyl methyl ether (Aldrich, 1.04 mL, 11.1 mmol) and potassium carbonate (1.97 g, 14.2 mmol) were mixed into DMF (8 mL). The suspention was stirred at 45° C. for 1 h. The temperature was raised to 55° C. for 45 min. 2-Bromoethyl methyl ether (0.50 mL) was added and the mixture was stirred at 40° C. for overnight. The reaction mixture was poured into about 50 mL water and the aqueous phase was extracted with diethyl ether (2×40 mL). The aqueous phase was saturated with solid NaCl and extracted with diethyl ether (2×40 mL). The combined organic phases were washed with saturated aqueous sodium bicarbonate (2×50 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. The light brown oil was placed under an air stream for 30 min to remove residual ether to afford 2-fluoro-5-(2-methoxyethoxy)pyridine (1.64 g, 100% yield) as an amber oil. 1H NMR (400 MHz, CDCl3) δ ppm 7.84-7.87 (m, 1H) 7.37 (ddd, J=9.05, 6.21, 3.13 Hz, 1H) 6.85 (dd, J=8.80, 3.52 Hz, 1H) 4.13-4.17 (m, 2H) 3.74-3.78 (m, 2H) 3.45 (s, 3H). m/z (ESI, positive ion): 172.1 (M+H)+.

Provenance & Evidence