Diethyl Ether → HCID 86663032, compound

Participants

Reaction Steps

Methyl 3-amino-6-bromo-2-(4-(hydroxymethyl)phenyl)isonicotinate (5.7 g, 16.91 mmol) was dissolved in TFA (85 mL) and the solution was cooled in an ice bath. Sodium nitrite (2.57 g, 37 2 mmol) was added slowly with stirring to give a yellow solution with gas evolution. After 40 min, gas evolution had ceased and solid sodium azide (10.99 g, 169 mmol) was added in portions over about 5 min with gas evolution. Et2O (85 mL) was slowly added and a precipitate formed. After stirring for 0.5 hr, water was added and the mixture was extracted with EtOAc. The combined organic phases were washed with water (3×) and brine (1×) and then 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 40 to 0% hexane and then 10% EtOAc) afforded methyl 3-azido-6-bromo-2-(4-formylphenyl)isonicotinate (4.45 g, 12.3 mmol, 73% yield) as a fluffy yellow solid. 1H NMR (500 MHz, chloroform-d) δ ppm 10.10 (1H, s), 7.96-8.04 (2H, m), 7.90-7.96 (2H, m), 7.86 (1H, s), 4.03 (3H, s).

Provenance & Evidence