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) was 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 the reaction mixture reached approximately 50° C. The mixture was then stirred at 52° C. for approximately 2 hours. The reaction was cooled to room temperature, then N,O-dimethylhydroxylamine hydrochloride (3.54 g, 35.6 mmol) was 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 and the layers separated. The acidic layer was extracted twice with dichloromethane and the organics combined. The organics 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. customreached approximately 50° C
2. temperatureThe reaction was cooled to room temperature
3. waitportion wise over approximately 15 minutes
4. additionafter each addition
5. stirringThe contents were stirred at room temperature overnight
6. customThe organic phase was then separated
7. extractionthe aqueous phase was extracted twice with dichloromethane
8. washThe combined organics were washed with 2 M aqueous hydrochloric acid
9. customthe layers separated
10. extractionThe acidic layer was extracted twice with dichloromethane
11. washThe organics were washed with a saturated, aqueous NaHCO3 solution
12. dry with materialdried over MgSO4
13. filtrationfiltered
14. customthe solvent was removed by distillation under reduced pressure

ORD-Eintrag

ord-b579b6a198bc4fe79eb8424a80689813

Quelldatensatz

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09284308B2