Acetic Acid → Ethyl 4-(2-fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxylate

Participants

Reaction Steps

6-Chloro-4-(2-fluoro-4-iodo-phenylamino)-nicotinic acid ethyl ester (15.0 g, 35.70 mmol) was dissolved in CHCl3 (100 mL) and the solution cooled (ice/water). Dimethyl sulfate (20.25 mL, 214.0 mmol) was added, the solution allowed to warm to room temperature then heated at reflux for 20 h. The reaction mixture was allowed to cool to room temperature, then a mixture of triethylamine (60.0 mL), acetic acid (20.0 mL) and EtOH (20.0 mL) added and the reaction heated at reflux for a further 2 h. After cooling, water (50 mL) was added and the mixture was partitioned between EtOAc (400 mL) and water (100 mL). The EtOAc layer was washed with further water (100 mL) and brine (100 mL), then dried (MgSO4). The solvent was removed under reduced pressure and the resulting residue purified by chromatography on silica gel (5% MeOH/CH2CCl2 as eluant), giving ethyl 4-(2-fluoro-4-iodoanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxylate as a white solid (10.48 g, 70%). 1H NMR [(CD3)2SO, 400 MHz] δ 9.31 (s, 1H), 8.54 (s, 1H), 7.77 (dd, J=10.1, 1.9 Hz, 1H), 7.60 (br dd, J=8.3, 1.0 Hz, 1H), 7.30 (t, J=8.5 Hz, 1H), 5.46 (s, 1H), 4.30 (q, J=7.1 Hz, 2H), 3.43 (s, 3H), 1.32 (t, J=7.1 Hz, 3H). Anal. Calcd for C15H14FIN2O3: C, 43.29; H, 3.39; N, 6.73. Found: C, 43.69; H, 3.26; N, 6.69.

Provenance & Evidence