Cesium carbonate → 3-Amino-5-bromo-1-methyl-1,2-dihydropyridin-2-one

Temperatur

95 °C

A 48-mL sealed tube equipped with a magnetic stirring bar was charged with benzophenone imine (0.43 g, 2.4 mmol), 3,5-dibromo-1-methyl-1H-pyridin-2-one (1) (0.51 g, 2.0 mmol), Pd(OAc)2 (0.025 g, 0.040 mmol), rac-BINAP (0.082 g, 0.13 mmol), and Cs2CO3 (0.92 g, 2.8 mmol) in dioxane (15 mL). After the mixture was degassed for 15 min., it was heated at 95° C. for 16 h. Then, the reaction mixture was cooled to room temperature and poured into H2O (10 mL). To this was added dichloromethane and the layers were separated. The aqueous phase was extracted with dichloromethane (3×10 mL), and the combined organic extracts were washed with H2O (5 mL) and brine (5 mL), dried (Na2SO4), and concentrated. The crude product was dissolved in 1 N HCl/MeOH (3 mL) and stirred for 1 h at room temperature. Then, to the reaction mixture was added sat. NaHCO3 (10 mL) and dichloromethane (10 mL), and the phases were separated. The aqueous layer was extracted with dichloromethane, and the combined organic layers were washed with H2O (5 mL) and brine (5 mL), dried (Na2SO4), and concentrated. The crude mixture was purified by column chromatography, gradient 0-10% MeOH in dichloromethane/ether (1/1), to afford 0.22 g (54%) of 3-amino-5-bromo-1-methyl-1H-pyridin-2-one (4) as a solid.

1. customA 48-mL sealed tube
2. customequipped with a magnetic stirring bar
3. customAfter the mixture was degassed for 15 min.
4. temperatureThen, the reaction mixture was cooled to room temperature
5. additionpoured into H2O (10 mL)
6. additionTo this was added dichloromethane
7. customthe layers were separated
8. extractionThe aqueous phase was extracted with dichloromethane (3×10 mL)
9. washthe combined organic extracts were washed with H2O (5 mL) and brine (5 mL)
10. dry with materialdried (Na2SO4)
11. concentrationconcentrated
12. dissolutionThe crude product was dissolved in 1 N HCl/MeOH (3 mL)
13. additionThen, to the reaction mixture was added sat. NaHCO3 (10 mL) and dichloromethane (10 mL)
14. customthe phases were separated
15. extractionThe aqueous layer was extracted with dichloromethane
16. washthe combined organic layers were washed with H2O (5 mL) and brine (5 mL)
17. dry with materialdried (Na2SO4)
18. concentrationconcentrated
19. customThe crude mixture was purified by column chromatography, gradient 0-10% MeOH in dichloromethane/ether (1/1)

ORD-Eintrag

ord-0ad029424ffd4e81b351c1c991fe6599

Quelldatensatz

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08058446B2