Diethyl Ether → HCID 86663037, compound

Participants

Reaction Steps

Methyl 3-amino-6-bromo-2-(3-(hydroxymethyl)phenyl)isonicotinate (1.35 g, 4.00 mmol) was dissolved in TFA (20 mL) and the yellow solution was cooled in an ice bath. Solid sodium nitrite (0.553 g, 8.01 mmol) was added with stirring to give a yellow solution with gas evolution. After 30 min, sodium azide (2.60 g, 40 0 mmol) was added over 5 min followed immediately by Et2O (20 mL). A precipitate formed and, after 0.5 hr, water was added and the mixture was extracted with EtOAc. The organic phases were washed with water (3×), brine (1×), and then saturated Na2CO3 solution (until the aqueous phase was basic) and brine (1×). After drying with sodium sulfate, the solvent was removed. Flash chromatography (step gradient elution with DCM containing 20% hexane, DCM and DCM containing 5% EtOAc) afforded methyl 3-azido-6-bromo-2-(3-formylphenyl)isonicotinate (0.90 g, 2.5 mmol, 63% yield) as a tan solid. 1H NMR (400 MHz, chloroform-d) δ ppm 10.09 (1H, s), 8.27 (1H, t, J=1.51 Hz), 8.01-8.07 (1H, m), 7.98 (1H, ddd, J=7.68, 1.51, 1.38 Hz), 7.84 (1H, s), 7.65 (1H, t, J=7.68 Hz), 4.02 (3H, s).

Provenance & Evidence