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

Temperature

0 °C

To a stirred solution of methyl-2-aminopyridine-4-carboxylate (35) (1.00 g, 6.57 mmol) in THF (100 mL), at −78° C. under nitrogen, was added methyllithium (1.6 M in diethyl ether, 16.4 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 (3×100 mL), and the combined organic extracts were dried and the solvents removed in vacuo. The crude residue was purified by column chromatography (SiO2, 80 g, 0-8% MeOH in EtOAc, gradient elution) to give the title compound (36) (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 (3×100 mL)
8. customthe combined organic extracts were dried
9. customthe solvents removed in vacuo
10. customThe crude residue was purified by column chromatography (SiO2, 80 g, 0-8% MeOH in EtOAc, gradient elution)

ORD record

ord-36dc3753106e45d183139e0f539439a9

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08299073B2