Potassium Carbonate → 4-(4-Amino-3-fluorophenoxy)picolinonitrile

Participants

Reaction Steps

A teflon capped vial was charged with 4-amino-3-fluorophenol (0.291 g, 2.29 mmol) and anhydrous DMF (2.3 mL). The resultant solution was de-gassed in vacuo and backfilled with argon (3×). The vial was treated with sodium tert-butoxide (0.27 g, 2.41 mmol) under argon and quickly capped. The reaction mixture was stirred at RT for 1 h. After addition of 4-chloropicolinonitrile (0.317 g, 2.29 mmol) and K2CO3 (0.174 g, 1.26 mmol), the vial was de-gassed again and heated in a 90° C. oil bath overnight. The reaction mixture was diluted with EtOAc (60 mL) and washed with brine (25 mL). The aqueous phase was back-extracted with EtOAc (50 mL). The combined organic layers were washed with brine (25 mL), dried (MgSO4), concentrated in vacuo and purified by chromatography to afford 4-(4-amino-3-fluorophenoxy)picolinonitrile (0.162 g, 31% yield) as a colorless oil. 1H NMR (DMSO-d6) δ 8.56 (d, J=5.6 Hz, 1H), 7.62 (d, J=2.0 Hz, 1H), 7.14 (dd, J=6.0, 2.8 Hz, 1H), 7.03 (dd, J=11.6, 2.4 Hz, 1H), 6.88-6.77 (m, 2H), 5.25 (s, 2H); MS (ESI) m/z: 230.0 (M+H+).

Provenance & Evidence