Diethyl Ether → Methyl 3-azido-6-bromo-6'-morpholino-2,3'-bipyridine-4-carboxylate

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Reaction Steps

Methyl 3-amino-6-bromo-6′-morpholino-2,3′-bipyridine-4-carboxylate (230 mg, 0.59 mmol) was dissolved in TFA (2.9 mL) and the solution was cooled in an ice bath. Solid sodium nitrite (89 mg, 1.29 mmol) was added slowly with stirring to give a red solution. After 30 min, powdered sodium azide (380 mg, 5.85 mmol) was added in portions with gas evolution. Et2O (29 mL) was added with stirring after 0.5 hr, water was added and the mixture was extracted with EtOAc. The combined organic extracts were washed with, water (3×), saturated Na2CO3 solution (until the aqueous phase was basic), and brine (1×). After drying the solvent with sodium sulfate, the solvent was removed. Flash chromatography (step gradient elution with DCM containing 0 to 20% EtOAc) afforded methyl 3-azido-6-bromo-6′-morpholino-2,3′-bipyridine-4-carboxylate (240 mg, 0.57 mmol, 98% yield) yellow solid. 1H NMR (500 MHz, chloroform-d) δ ppm 8.73 (1H, d, J=2.44 Hz), 7.99 (1H, dd, J=9.00, 2.59 Hz), 7.71 (1H, s), 6.68 (1H, d, J=8.85 Hz), 4.00 (3H, s), 3.79-3.86 (4H, m), 3.59-3.66 (4H, m).

Provenance & Evidence