2-Fluoro-4-iodoaniline → Ethyl 6-chloro-4-(2-fluoro-4-iodoanilino)nicotinate

Participants

Reaction Conditions

Reaction Steps

Ethyl 4,6-dichloronicotinate [prepared according to the literature procedure of J. Chem. Soc. 5163 (1963)] (4.00 g, 18.2 mmol) and 2-fluoro-4-iodoaniline (4.30 g, 18.2 mmol) were dissolved in EtOH (80 mL), to which was added conc. HCl (6 drops). This mixture was heated, in an oil bath at 90° C., for 15 h. The solution was allowed to cool, then refrigerated whereupon the desired product crystallised out of solution as fine needles. The product was isolated by filtration and washed with 10% Et2O/hexanes to give ethyl 6-chloro-4-(2-fluoro-4-iodoanilino)nicotinate as white needles (3.79 g, 50%), m.p. (EtOAc/n-hexane) 162-164° C. 1H NMR [(CD3)2SO, 400 MHz] δ 9.62 (s, 1H), 8.69 (s, 1H), 7.82 (dd, J=9.9, 1.9 Hz, 1H), 7.61-7.66 (m, 1H), 7.33 (t, J=8.5 Hz, 1H), 6.67 (d, J=1.8 Hz, 1H), 4.37 (q, J=7.1 Hz, 2H), 1.35 (t, J=7.1 Hz, 3H). Anal. Calcd for C14H11ClFIN2O2: C, 40.0; H, 2.6; N, 6.7. Found: C, 40.3; H, 2.2; N, 6.7.

Provenance & Evidence