Carbon Dioxide → N-Methoxy-N-methylpyrimidine-2-carboxamide

Temperatur

52 °C

Sodium pyrimidine-2-carboxylate (4.00 g, 27.4 mmol), imidazole hydrochloride (3.15 g, 30.1 mmol), and 1-carbonyldiimidazole (5.26 g, 31.5 mmol) were slurried in acetonitrile (30 mL) at room temperature under an N2 atmosphere. The mixture was then warmed to 52° C. over 30 minutes. Evolution of carbon dioxide was seen when reaction mixture reached approximately 50° C. The mixture was then stirred at 52° C. for approximately 2 hours. The reaction was then cooled to room temperature, then N,O-dimethylhydroxylamine hydrochloride (3.54 g, 35.6 mmol) was then added slowly, portion wise over approximately 15 minutes and a mild exotherm was seen after each addition. The contents were stirred at room temperature overnight. To the reaction mixture was then added deionized water (25 mL) and dichloromethane (25 mL). 6 M Aqueous hydrochloric acid was added dropwise to acidify the aqueous layer to approximately pH 1. The organic phase was then separated and the aqueous phase was extracted twice with dichloromethane. The combined organics were washed with 2 M aqueous hydrochloric acid, separated, then the acidic layer was extracted twice with dichloromethane. The combined organic phases were washed with a saturated, aqueous NaHCO3 solution, then dried over MgSO4, filtered and the solvent was removed by distillation under reduced pressure to provide the title compound.

1. customwhen reaction mixture
2. customreached approximately 50° C
3. temperatureThe reaction was then cooled to room temperature
4. waitportion wise over approximately 15 minutes
5. additionafter each addition
6. stirringThe contents were stirred at room temperature overnight
7. customThe organic phase was then separated
8. extractionthe aqueous phase was extracted twice with dichloromethane
9. washThe combined organics were washed with 2 M aqueous hydrochloric acid
10. customseparated
11. extractionthe acidic layer was extracted twice with dichloromethane
12. washThe combined organic phases were washed with a saturated, aqueous NaHCO3 solution
13. dry with materialdried over MgSO4
14. filtrationfiltered
15. customthe solvent was removed by distillation under reduced pressure

ORD-Eintrag

ord-4f0f9638934b47fd9332aa47a20a99c2

Quelldatensatz

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09403816B2