反应详情

Ethyl 2-methylacetoacetate (50 g) in DMF (25 ml) was added to a suspension of sodium hydride (12.0 g of 60% NaH in mineral oil) in DMF (100 ml), dropwise with ice-bath cooling over 1 hour, (internal temperature 0-4° C.). This mixture was allowed to warm to ambient temperature for 45 mins with stirring before re-cooling. A solution of 1,4-butanesultone (45 g) in DMF (25 ml) was then added dropwise over 15 minutes. The final mixture was heated at 60° C. for 18 hours. The solvent was removed by rotary evaporation and the residue partitioned between water and diethyl ether. The aqueous layer was collected, washed with fresh diethyl ether and rotary evaporated to yield a sticky foam. This intermediate was dissolved in water (100 ml) and sodium hydroxide (17.8 g) added over 15 minutes with stirring. The mixture was heated at 90° C. for 18 hours. The cooled reaction mixture was adjusted to ˜pH2 by the addition of concentrated hydrochloric acid (˜40 ml). The solution was rotary evaporated and dried under vacuum. The yellow solid was washed with ethanol containing 2% hydrochloric acid (3×150 ml). The ethanolic solution was filtered, rotary evaporated and dried under vacuum to yield a yellow solid. Yield 70 g.

1. temperaturecooling over 1 hour
2. custom(internal temperature 0-4° C.)
3. temperaturebefore re-cooling
4. customThe solvent was removed by rotary evaporation
5. customthe residue partitioned between water and diethyl ether
6. customThe aqueous layer was collected
7. washwashed with fresh diethyl ether
8. customrotary evaporated
9. customto yield a sticky foam
10. stirringwith stirring
11. temperatureThe mixture was heated at 90° C. for 18 hours
12. customThe cooled reaction mixture
13. customThe solution was rotary evaporated
14. customdried under vacuum
15. washThe yellow solid was washed with ethanol containing 2% hydrochloric acid (3×150 ml)
16. filtrationThe ethanolic solution was filtered
17. customrotary evaporated
18. customdried under vacuum
19. customto yield a yellow solid