Acetic Acid → 6-Chloro-2-methoxypyridine-3-carbaldehyde

Temperature

-78 °C

To a solution of tert-butyllithium (1.7 M in pentane, 48.5 mL, 83.0 mmol) in 150 mL of THF at -78° C. was added 6-chloro-2-methoxypyridine (8.94 mL, 75.0 mmol) over 5 min. The reaction mixture was stirred at -78° C. for 1 h, then dimethylformamide (7.55 mL, 97 mmol) was added and the mixture was stirred at this temperature for 1.5 h. After the addition of glacial acetic acid (8.6 mL, 150 mmol), the reaction mixture was allowed to warm to room temperature over a 30- min period, then diluted with ether (200 mL). The organic phase was washed with saturated aqueous NaHCO3 (100 mL) and brine (100 mL), and was dried over MgSO4. Concentration afforded the crude product as a light yellow solid which was recrystallized from hexanes to give 9.6 g (75%) of 6-chloro-2-methoxy-3-pyridinecarboxaldehyde as a white solid: mp 80°-81° C. (mp Suschitzky, H.; Wakefield, B. J. Tetrahedron Lett. 1984, 25, 5693.). 1H NMR (300 MHz, CDCl3)δ10.31 (s, 1H), 8.07 (d, IH, J =9 Hz), 7.03 (d, 1H, J =9 Hz), 4.09 (s, 3H); IR (nujol) 1685, 1580, 1565, 1270, 1140, 1090, 1005, 905, 820, 755 cm-1.

1. stirringthe mixture was stirred at this temperature for 1.5 h
2. temperatureto warm to room temperature over a 30- min period
3. washThe organic phase was washed with saturated aqueous NaHCO3 (100 mL) and brine (100 mL)
4. dry with materialwas dried over MgSO4
5. concentrationConcentration
6. customafforded the crude product as a light yellow solid which
7. customwas recrystallized from hexanes

ORD record

ord-63b9b2d355cb436f8db69da91037fe95

Source dataset

uspto-grants-1993_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05247089