Diethyl Ether → Methyl 3-azido-6-(3-fluoro-4-methoxyphenyl)-2-(4-(methoxycarbonyl)phenyl)isonicotinate

Participants

Reaction Steps

Methyl 3-amino-6-(3-fluoro-4-methoxyphenyl)-2-(4-(methoxycarbonyl)phenyl)-isonicotinate (1.00 g, 2.44 mmol) was dissolved in trifluoroacetic acid (12 mL) and the yellow solution was cooled in an ice bath. Powdered sodium nitrite (0.336 gm, 4.87 mmol) was added with stirring to give a dark red mixture. After 30 min, powdered sodium azide (1.59 g, 24.4 mmol) was added followed by diethyl ether (12 mL). The light red mixture was stirred in the ice bath for 30 min. The reaction was partitioned between EtOAc and sufficient saturated aqueous NaHCO3 solution (gas evolution) to neutralize the acid. The organic phase was washed with brine, dried with sodium sulfate, and the solvent removed. Flash silica gel chromatography (elution with a 1:1 mixture of methylene chloride and EtOAc) afforded methyl 3-azido-6-(3-fluoro-4-methoxyphenyl)-2-(4-(methoxycarbonyl)phenyl)isonicotinate (1.06 gm). 1H NMR (CDCl3) δ ppm 8.17 (2H, d, J=7.93 Hz), 8.01 (1H, s), 7.91 (2H, d, J=7.93 Hz), 7.82-7.88 (1H, m), 7.79 (1H, d, J=8.55 Hz), 7.04 (1H, t, J=8.55 Hz), 4.05 (3H, s), 3.96 (3H, s), 3.94 (3H, s).

Provenance & Evidence