Diethyl Ether → Methyl 3-azido-6-bromo-2-(4-(morpholinosulfonyl)phenyl)isonicotinate

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Reaction Steps

Methyl 3-amino-6-bromo-2-(4-(morpholinosulfonyl)phenyl)-isonicotinate (0.988 g, 2.17 mmol) was dissolved in TFA (11 mL) and the yellow solution was cooled in an ice bath. Powdered sodium nitrite (0.299 g, 4.33 mmol) was added with stirring to give a dark red mixture with gas evolution. After 20 min, powdered sodium azide (1.41 g, 21.7 mmol) was added over 5 min followed by Et2O (11 mL). A thick precipitate formed and, after 30 min, water was added and the mixture was extracted with EtOAc. The organic phase was washed with water (3×), brine (1×), saturated aqueous Na2CO3 solution (so that the aqueous phase was basic), and brine. After drying the solvent with sodium sulfate, the solvent was removed and silica gel chromatography (step gradient elution with DCM containing 0 to 10% EtOAc) afforded methyl 3-azido-6-bromo-2-(4-(morpholinosulfonyl)phenyl)isonicotinate (918 mg, 1.90 mmol, 88% yield). 1H NMR (500 MHz, chloroform-d) δ ppm 7.93-7.96 (2H, m), 7.87 (1H, s), 7.85 (2H, d, J=8.24 Hz), 4.03 (3H, s), 3.73-3.77 (4H, m), 3.03-3.07 (4H, m).

Provenance & Evidence