反応 #2195496

反応方程式

trimethylaluminum

trimethylaluminum

benzylamine

product

Diethyl 2,2,3,3,4,4,-hexafluoropentanedioate

sodium hydride

→

title compound

1-Benzyl-3,3,4,4,5,5-hexafluoropiperidine-2,6-dione

溶媒

water

hexane

methylene chloride

methylene chloride

反応条件

後処理

1. 1
   温度cool in an ice/water bath under argon
2. 2
   workup.STIRRINGRemove ice bath and stir for 2 h at room temperature
3. 3
   温度heat
4. 4
   温度under reflux for 3 h
5. 5
   温度Cool in an ice/water bath
6. 6
   その他Partition the reaction mixture between 30 mL each of ether and water
7. 7
   洗浄wash the organic layer with 1N HCl, saturated sodium bicarbonate, and brine
8. 8
   乾燥dry over MgSO4
9. 9
   濃縮concentrate in vacuo
10. 10
    workup.DISSOLUTIONDissolve the residue in 2 mL of DMF
11. 11
    洗浄washed with hexane twice
12. 12
    その他to remove mineral oil) and 4 mL of DMF under argon
13. 13
    workup.STIRRINGStir for 16 h at room temperature
14. 14
    その他Cautiously decompose excess sodium hydride with several drops of water and partition the mixture between ethyl acetate and water
15. 15
    抽出Extract the aqueous layer twice with more ethyl acetate
16. 16
    洗浄wash the combined organic layers with 1N HCl, saturated sodium bicarbonate, and brine
17. 17
    乾燥Dry over MgSO4
18. 18
    濃縮concentrate in vacuo
19. 19
    その他Purify the residue by silica gel chromatography

実験手順

Dissolve 3.4 mmol of benzylamine in 12 mL of methylene chloride and cool in an ice/water bath under argon. Add 4.1 mmol of trimethylaluminum as a 2 M hexane solution dropwise during several minutes. Stir for 10 min, then add 3.4 mmol of the product of Example 7 as a solution in 4 mL of methylene chloride. Remove ice bath and stir for 2 h at room temperature, then heat under reflux for 3 h. Cool in an ice/water bath and cautiously decompose excess trimethylaluminum with water. Partition the reaction mixture between 30 mL each of ether and water and wash the organic layer with 1N HCl, saturated sodium bicarbonate, and brine, then dry over MgSO4 and concentrate in vacuo. Dissolve the residue in 2 mL of DMF and add to a slurry of 3.5 mmol of sodium hydride (washed with hexane twice to remove mineral oil) and 4 mL of DMF under argon. Stir for 16 h at room temperature. Cautiously decompose excess sodium hydride with several drops of water and partition the mixture between ethyl acetate and water. Extract the aqueous layer twice with more ethyl acetate, then wash the combined organic layers with 1N HCl, saturated sodium bicarbonate, and brine. Dry over MgSO4 and concentrate in vacuo. Purify the residue by silica gel chromatography using ethyl acetate/hexanes eluant to yield the title compound.

出典