Phenol → Methyl 2-(phenoxymethyl)isonicotinate

Participants

Reaction Steps

Methyl 2-(hydroxymethyl)isonicotinate (2.232 g, 13.35 mmol) dissolved in THF (15 mL) and phenol (1.426 mL, 16.02 mmol) and triphenylphosphine (3.71 mL, 16.02 mmol) were added. The mixture was cooled to 0° C. (E)-diisopropyl diazene-1,2-dicarboxylate (3.24 g, 16.02 mmol) was added dropwise, the ice-bath removed and the reaction stirred at room temperature for 2 h. The solvent was evaporated and the residue was purified by automated flash chromatography on a Biotage® KP-SIL 340 g column. 4:1 of EtOAc in heptane over 10 CV was used as mobile phase. Methyl 2-(phenoxymethyl)isonicotinate (2.65 g, 82%) was isolated. 1H NMR (400 MHz, cdcl3) δ 3.96 (s, 3H), 5.26 (s, 2H), 6.95-7.04 (m, 3H), 7.27-7.34 (m, 2H), 7.76-7.80 (m, 1H), 8.10 (s, 1H), 8.75 (d, 1H). MS m/z 244 (M+H)+

Provenance & Evidence