2-Aminonicotinic acid → (2-Aminopyridin-3-yl)methanol

Temperature

0 °C

To a stirred solution of 2-aminonicotinic acid (20 g, 145 mmole) in dry THF (200 mL) under argon was added 1.0 M LiAlH4 in THF (300 mL, 300 mmole) carefully, portionwise, through a reflux condenser, over 4 hr. The reaction became exothermic and refluxed without external heating. After the addition was complete, the reaction was heated at reflux for an additional 16 hr, then was cooled to 0° C. and carefully quenched by sequential addition of H2O (12 mL), 15% NaOH in H2O (12 mL), and H2O (35 mL). The resulting thick suspension was stirred for 1 hr, then was filtered through a pad of celite®. The filter pad was rinsed with THF (300 mL), and the filtrate was concentrated to dryness to give the title compound (17.04 g, 95%) as a pale yellow waxy solid: LCMS (ES) m/e 125.1 (M+H)+; 1H NMR (400 MHz, DMSO-d6) δ 7.84 (dd, 1 H), 7.37 (m, 1 H), 6.53 (dd, 1 H), 5.65 (br s, 2 H), 5.16 (t, 1 H), 4.34 (d, J=4.6 Hz, 2 H).

1. temperaturerefluxed without external heating
2. additionAfter the addition
3. temperaturethe reaction was heated
4. temperatureat reflux for an additional 16 hr
5. customcarefully quenched by sequential addition of H2O (12 mL), 15% NaOH in H2O (12 mL), and H2O (35 mL)
6. filtrationwas filtered through a pad of celite®
7. washThe filter pad was rinsed with THF (300 mL)
8. concentrationthe filtrate was concentrated to dryness

ORD record

ord-3fadf42c2263436e8dedcaf2f515e749

Source dataset

uspto-grants-2009_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07557125B2