Water → 1-(2-Amino-4,6-dichloropyrimidin-5-yl)-2-(2,2-dimethyl-[1,3]dioxolan-4-yl)ethan-1-ol

A mixture composed of 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 2 days. After the disappearance of the materials had been confirmed, a saturated aqueous sodium thiosulfate solution (1 L) was added to the reaction solution, and the reaction mixture was then concentrated to approximately 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. After filtration, the filtrate was concentrated under reduced pressure, and the solvent was then distilled away. N,N-Dimethylformamide (500 ml), 2,2-dimethoxypropane (210 ml) and p-toluenesulfonic acid monohydrate (18.61 g) were added to the resulting residue. The resulting 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 successively washed with water and saturated saline in this order, and it was then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated to about 100 ml under reduced pressure. Hexane was added to the residue, and the precipitate was then collected by filtration, so as to obtain the title compound (53.88 g) as a solid.

1. concentrationthe reaction mixture was then concentrated to approximately 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. filtrationAfter filtration
5. concentrationthe filtrate was concentrated under reduced pressure
6. distillationthe solvent was then distilled away
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 resulting 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 successively washed with water and saturated saline in this order, and it
12. dry with materialwas then dried 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. filtrationthe precipitate was then collected by filtration

ORD-Eintrag

ord-0ccc7012debd4ad793545c4e9643a0c8

Quelldatensatz

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08236813B2