反应详情

A mixture composed of the above 1-(2-amino-4,6-dichloropyrimidin-5-yl)-3-buten-1-ol (57.24 g), N-methylmorpholine-N-oxide (147.6 g), tetrahydrofuran (500 mL), acetone (500 mL), water (500 mL) and osmium tetroxide (62 mg) was stirred at room temperature for two days. After confirming that the raw material disappeared, a saturated sodium thiosulfate solution (1 L) was added, and the reaction mixture was concentrated to about 1.5 L under reduced pressure. The residue was saturated with sodium chloride, followed by extraction with tetrahydrofuran. The organic layer was dried over anhydrous sodium sulfate and filtered. Then, the filtrate was concentrated under reduced pressure to evaporate the solvent. N,N-Dimethylformamide (500 mL), 2,2-dimethoxypropane (210 mL) and p-toluenesulfonic acid monohydrate (18.61 g) were added to the resulting residue, and the mixture was stirred at room temperature for 14 hours. A saturated sodium bicarbonate solution (1 L) and water (1 L) were added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was sequentially washed with water and brine and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated to about 100 mL under reduced pressure. Hexane was added to the residue, followed by stirring. The precipitated crystals were collected by filtration to obtain the title compound (53.88 g, 77%) as a solid.

1. concentrationthe reaction mixture was concentrated to about 1.5 L under reduced pressure
2. extractionfollowed by extraction with tetrahydrofuran
3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
4. filtrationfiltered
5. concentrationThen, the filtrate was concentrated under reduced pressure
6. customto evaporate the solvent
7. additionN,N-Dimethylformamide (500 mL), 2,2-dimethoxypropane (210 mL) and p-toluenesulfonic acid monohydrate (18.61 g) were added to the resulting residue
8. stirringthe mixture was stirred at room temperature for 14 hours
9. additionA saturated sodium bicarbonate solution (1 L) and water (1 L) were added to the reaction mixture
10. extractionfollowed by extraction with ethyl acetate
11. washThe organic layer was sequentially washed with water and brine
12. dry with materialdried over anhydrous sodium sulfate
13. filtrationAfter filtration
14. concentrationthe filtrate was concentrated to about 100 mL under reduced pressure
15. additionHexane was added to the residue
16. stirringby stirring
17. filtrationThe precipitated crystals were collected by filtration