Hydrochloric Acid → Methyl 3-azido-2,6-bis(4-methoxyphenyl)isonicotinate

Participants

Reaction Steps

Methyl 3-amino-2,6-bis(4-methoxyphenyl)isonicotinate (234 mg, 0.642 mmol) was dissolved with heating in ethanol (8 mL). After cooling to room temperature, 17% aqueous HCl (4 mL) was added and the reaction was cooled in an ice bath. Sodium nitrite (70.9 mg, 1.027 mmol) was added and the solution turned orange-red. After 25 min, sodium azide (66.8 mg, 1.027 mmol) was added and, after a further 20 min, the reaction was removed from the bath and left stirring at room temperature for 1 hr. The reaction was partitioned between ethyl acetate and sufficient saturated aqueous sodium bicarbonate solution to neutralize the acid. The organic phase was separated, washed with brine, and dried with sodium sulfate. Radial silica gel chromatography (step gradient elution with hexane containing 5 to 20% ethyl acetate) afforded methyl 3-azido-2,6-bis(4-methoxyphenyl)isonicotinate (105 mg, 42% yield) as a yellow solid. MS (ESI) m/z 391.1 (M+H). 1H NMR (CDCl3) δ ppm 8.03 (2H, d, J=8.85 Hz), 7.93 (1H, s), 7.83 (2H, d, J=8.85 Hz), 7.02 (2H, d, J=8.85 Hz), 6.98 (2H, d, J=9.16 Hz), 4.03 (3H, s), 3.88 (3H, s), 3.86 (3H, s).

Provenance & Evidence