反応 #68705

反応方程式

hydrochloric acid

sodium hydroxide

Ethyl 2-methylacetoacetate

sodium hydride

1,4-butanesultone

→

5-Methyl-6-oxoheptane-1-sulfonic acid

溶媒

water

DMF

DMF

DMF

反応条件

後処理

1. 1
   温度cooling over 1 hour
2. 2
   その他(internal temperature 0-4° C.)
3. 3
   温度before re-cooling
4. 4
   その他The solvent was removed by rotary evaporation
5. 5
   その他the residue partitioned between water and diethyl ether
6. 6
   その他The aqueous layer was collected
7. 7
   洗浄washed with fresh diethyl ether
8. 8
   その他rotary evaporated
9. 9
   その他to yield a sticky foam
10. 10
    workup.STIRRINGwith stirring
11. 11
    温度The mixture was heated at 90° C. for 18 hours
12. 12
    その他The cooled reaction mixture
13. 13
    その他The solution was rotary evaporated
14. 14
    その他dried under vacuum
15. 15
    洗浄The yellow solid was washed with ethanol containing 2% hydrochloric acid (3×150 ml)
16. 16
    ろ過The ethanolic solution was filtered
17. 17
    その他rotary evaporated
18. 18
    その他dried under vacuum
19. 19
    その他to yield a yellow solid

実験手順

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.

出典