N,N'-Dimethylethylenediamine → Methyl 2-fluoro-4-(2-oxo-1(2H)-pyridinyl)benzoate

Participants

Reaction Steps

A mixture of 4-bromo-2-fluoro-benzoic acid methyl ester (1.17 g, 5.0 mmol), 2-hydroxypyridine (0.72 g, 7.5 mmol, 1.5 eq), K2CO3 (1.38 g, 10.0 mmol, 2.0 eq), CuI (0.48 g, 2.5 mmol, 0.5 eq), and N,N′-dimethylethylenediamine (0.22 mL, 2.6 mmol, 0.5 eq) was heated in refluxing toluene (6 mL) for 8 h. After cooling, EtOAc was added. The mixture was filtered through a pad of silica gel and rinsed with EtOAc. The desired fractions were concentrated in vacuo to give essentially pure 2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-benzoic acid methyl ester (1.05 g, yield: 84%). 1H NMR (CDCl3) δ 8.07 (t, J=8.0 Hz, 1H), 7.14 (m, 1H), 7.33–7.27 (m, 3H), 6.64 (m, 1H), 6.28 (m, 1H), 3.96 (s, 3H) ppm. LC/MS (ESI) 248.05 (M+H), tR=2.05 min (10–90% MeOH in H2O with 10 mM NH4OAc in a 4-min run).

Provenance & Evidence