Boron trifluoride etherate → 3-Acetoxy-6-fluoropyridine

Participants

Reaction Conditions

Reaction Steps

A solution of 3-amino-6-fluoropyridine (5.0 g, 45 mmol, from Step 8c above) dissolved in DME (30 mL) was added to a cooled solution (-15° C.) of boron trifluoride etherate (12.2 mL, 99 mmol). tert-Butyl nitrite (6.3 mL, 54 mmol) was then added at a rate which maintained the temperature below 0° C. After 10 minutes at -10° C. the reaction was warmed to 5° C. and stirred for 30 min. Pentane (150 mL) was then added to the reaction mixture, and the resultant solid was collected by suction filtration, washed with cold ether, air dried, and dissolved in acetic anhydride (75 mL). The solution was heated to 105° C. until nitrogen evolution ceased. The solvent was removed in vacuo, and the residue was suspended in saturated aqueous Na2CO3 (200 mL) and extracted with ethyl ether (2×150 mL). The combined organic extracts were dried (MgSO4) and concentrated. Purification by chromatography (silica gel; hexane/EtOAc, 9:1 to 7:3) afforded the title compound (2.25 g, 33%): 1H NMR (CDCl3 300 MHz) δ 2.32 (s, 3H), 6.96 (d, J=3, 9 Hz, 1H), 7.59 (m, 1H), 8.03 (dd, J=0.5, 1 Hz, 1H); MS (CI/NH3) m/z 156 (M+H)+, 171 (M+NH4)+.

Provenance & Evidence