反应详情

温度

-78 °C

To a solution of diisopropylamine (0.39 mL, 4.2 mmol) in tetrahydrofuran (8 mL) at -78° C. under nitrogen atmosphere is added a 2.1M solution of n-butyllithium (2.0 mL, 4.2 mmol) in cyclohexane. This mixture is stirred at -78° C. for 1 hour and thiazole (0.3 mL, 4.2 mmol) added. After stirring 1 hour at -78° C., the reaction mixture is warmed to ~0° C. and stirred 0.5 hours. The mixture is cooled to -78° and 4,6-bis(1,1-dimethylethyl)-5-hydroxy-N-methoxy-N-methyl-2-pyrimidinecarboxamide (0.50 g, 1.7 mmol) in a mixture of tetrahydrofuran (5 mL) and N,N,N'N'-tetramethylethylenediamine (2 mL). After stirring 1 hour at 78° C., the resulting mixture is warmed to room temperature and stirred 16 hours. The mixture is then quenched with aqueous ammonium chloride solution and extracted with ethyl acetate. The combined extracts are washed with water and brine. The organic phase is dried over magnesium sulfate and concentrated under vacuum. The organic residue is purified by flash chromatography (SiO2, 10% methanol/dichloromethane) followed by recrystallization from ethyl acetate and hexane to give 0.30 g (53%) of the title compound, mp 181°-184° C.

1. stirringAfter stirring 1 hour at -78° C.
2. temperaturethe reaction mixture is warmed to ~0° C.
3. stirringstirred 0.5 hours
4. temperatureThe mixture is cooled to -78°
5. stirringAfter stirring 1 hour at 78° C.
6. temperaturethe resulting mixture is warmed to room temperature
7. stirringstirred 16 hours
8. customThe mixture is then quenched with aqueous ammonium chloride solution
9. extractionextracted with ethyl acetate
10. washThe combined extracts are washed with water and brine
11. dry with materialThe organic phase is dried over magnesium sulfate
12. concentrationconcentrated under vacuum
13. customThe organic residue is purified by flash chromatography (SiO2, 10% methanol/dichloromethane)
14. customfollowed by recrystallization from ethyl acetate and hexane