Methyl 2-aminopyridine-4-carboxylate → 1-(2-Aminopyridin-4-yl)ethan-1-one

Temperatur

0 °C

To a stirred solution of methyl-2-aminopyridine-4-carboxylate (20) (1.00 g, 6.57 mmol) in THF (100 mL), at −78° C. under nitrogen, was added methyllithium (1.6 M in diethyl ether, 16.43 ml, 26.3 mmol), over 10 min. After a further 30 min at −78° C., the viscous reaction mixture was warmed to 0° C. After a further 3 hr, the reaction was quenched at 0° C. by the cautious addition of iso-propanol (8.0 mL). The mixture was warmed to RT, brine (200 mL) and EtOAc (150 mL) were added, and the layers were separated. The aqueous layer was extracted with EtOAc (100 mL×3), and the combined organic extracts were dried and the solvents removed under reduced pressure. The crude residue was purified by column chromatography (80 g) eluting with 0 to 8% MeOH in EtOAc, to give 1-(2-aminopyridin-4-yl)ethanone (21) (176 mg, 20%) as a yellow powder: m/z 137 (M+H)+ (ES+).

1. waitAfter a further 30 min at −78° C.
2. waitAfter a further 3 hr
3. customthe reaction was quenched at 0° C. by the cautious addition of iso-propanol (8.0 mL)
4. temperatureThe mixture was warmed to RT
5. additionbrine (200 mL) and EtOAc (150 mL) were added
6. customthe layers were separated
7. extractionThe aqueous layer was extracted with EtOAc (100 mL×3)
8. customthe combined organic extracts were dried
9. customthe solvents removed under reduced pressure
10. customThe crude residue was purified by column chromatography (80 g)
11. washeluting with 0 to 8% MeOH in EtOAc

ORD-Eintrag

ord-1d73483c2d4d47bdb82ba7ca8c857bf3

Quelldatensatz

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08618140B2