Реакция #2195496

Уравнение реакции

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

Растворители

water

hexane

methylene chloride

methylene chloride

Условия реакции

Обработка

1. 1
   Температураcool in an ice/water bath under argon
2. 2
   workup.STIRRINGRemove ice bath and stir for 2 h at room temperature
3. 3
   Температураheat
4. 4
   Температураunder reflux for 3 h
5. 5
   ТемператураCool in an ice/water bath
6. 6
   ДругоеPartition the reaction mixture between 30 mL each of ether and water
7. 7
   Промывкаwash the organic layer with 1N HCl, saturated sodium bicarbonate, and brine
8. 8
   Сушкаdry over MgSO4
9. 9
   Концентрированиеconcentrate in vacuo
10. 10
    workup.DISSOLUTIONDissolve the residue in 2 mL of DMF
11. 11
    Промывкаwashed with hexane twice
12. 12
    Другоеto remove mineral oil) and 4 mL of DMF under argon
13. 13
    workup.STIRRINGStir for 16 h at room temperature
14. 14
    ДругоеCautiously decompose excess sodium hydride with several drops of water and partition the mixture between ethyl acetate and water
15. 15
    ЭкстракцияExtract the aqueous layer twice with more ethyl acetate
16. 16
    Промывкаwash the combined organic layers with 1N HCl, saturated sodium bicarbonate, and brine
17. 17
    СушкаDry over MgSO4
18. 18
    Концентрированиеconcentrate in vacuo
19. 19
    ДругоеPurify the residue by silica gel chromatography

Методика

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.

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