反应详情

温度

30 °C

[(4R,6S)-6-hydroxymethyl-2,2-dimethyl-[1,3]dioxan-4-yl]-acetic acid (50.0 g), acetonitrile (500.0 mL), and ammonium chloride (1.3 g) were added to a reactor. The reaction mixture was cooled to 0˜5° C. and then hexamethyldisilazane (102.1 mL) was slowly added thereto. The reaction mixture was stirred at 30° C. for 1 hour and then concentrated under reduced pressure to remove the solvent. Ethyl acetate (250.0 mL) and water (200.0 mL) were added to the resulting residue. The separated organic layer was dehydrated with anhydrous magnesium sulfate (50.0 g) and then filtered under reduced pressure. The filtrate was concentrated under reduced pressure to obtain a concentrated residue in a colorless clear oil form. Dichloromethane (250.0 mL) was added to the concentrated residue. The reaction mixture was cooled to 0˜5° C. and then 1,1′-carbonyldiimidazole (43.7 g) was slowly added thereto. The temperature of the reaction mixture was raised to 20˜25° C. The reaction mixture was stirred at the same temperature for 3 hours and then N,O-dimethylhydroxyamine hydrochloride (26.4 g) and sodium bicarbonate (22.6 g) were added thereto. The reaction mixture was stirred for over 10 hours, while maintaining the temperature of 20˜25° C. Water (250.0 mL) was added to the reaction mixture and then the resulting organic layer was separated. The water layer was extracted with dichloromethane (150.0 mL) to obtain an organic layer. The combined organic layer was dehydrated with anhydrous sodium sulfate (50.0 g) and then filtered under reduced pressure. The filtrate was concentrated under reduced pressure to remove the solvent, and then purified with silica gel column chromatography (ethyl acetate/n-hexane=1:4) to obtain 2-[(4R,6S)-6-hydroxymethyl-2,2-dimethyl-[1,3]dioxan-4-yl]-N-methoxy-N-methyl-acetamide in a colorless gel form (49.7 g, yield 82%).

1. temperatureThe reaction mixture was cooled to 0˜5° C.
2. concentrationconcentrated under reduced pressure
3. customto remove the solvent
4. additionEthyl acetate (250.0 mL) and water (200.0 mL) were added to the resulting residue
5. filtrationfiltered under reduced pressure
6. concentrationThe filtrate was concentrated under reduced pressure
7. customto obtain a concentrated residue in a colorless clear oil form
8. temperatureThe reaction mixture was cooled to 0˜5° C.
9. temperatureThe temperature of the reaction mixture was raised to 20˜25° C
10. stirringThe reaction mixture was stirred at the same temperature for 3 hours
11. stirringThe reaction mixture was stirred for over 10 hours
12. temperaturewhile maintaining the temperature of 20˜25° C
13. customthe resulting organic layer was separated
14. extractionThe water layer was extracted with dichloromethane (150.0 mL)
15. customto obtain an organic layer
16. filtrationfiltered under reduced pressure
17. concentrationThe filtrate was concentrated under reduced pressure
18. customto remove the solvent
19. custompurified with silica gel column chromatography (ethyl acetate/n-hexane=1:4)