Reaktion #549484

Reaktionsgleichung

ammonium chloride

magnesium

4-cyano-4-dimethylaminocyclohexanone ethylene ketal

hydrogen chloride

m-trifluoromethylbromobenzene

hydrogen chloride

→

4-(m-trifluoromethylphenyl)-4-dimethylaminocyclohexanone ethylene ketal hydrochloride

Ausbeute 24.0%

Lösungsmittel

diethyl ether

benzene

diethyl ether

tetrahydrofuran

tetrahydrofuran

ether

methylene chloride

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONto this is added 1.50 gm
2. 2
   workup.DISSOLUTIONdissolved in 40 ml
3. 3
   TemperaturThis reaction mixture is heated at the reflux temperature for 17 hours
4. 4
   TemperaturIt is then cooled
5. 5
   Temperaturchilled in ice
6. 6
   SonstigeThe organic solution is then separated
7. 7
   Wascheninitially washed with water
8. 8
   Waschenwashed with brine
9. 9
   SonstigeThe solvents are then removed by evaporation under reduced pressure
10. 10
    SonstigeThe residue thus obtained
11. 11
    SonstigeThe supernatant liquid is decanted
12. 12
    workup.DISSOLUTIONthe remaining gum is dissolved in methylene chloride
13. 13
    workup.ADDITIONOne N aqueous sodium hydroxide is added
14. 14
    SonstigeThe organic layer is then separated
15. 15
    Sonstigethe methylene chloride is removed by evaporation under reduced pressure
16. 16
    SonstigeThe residue thus obtained
17. 17
    Sonstigeare collected
18. 18
    SonstigeThe solvent is removed by evaporation under reduced pressure
19. 19
    Sonstigethe gummy residue thus obtained
20. 20
    SonstigeThe precipitate is collected on
21. 21
    Filtrationa filter
22. 22
    Sonstigerecrystallized from a mixture of methylene chloride and ethyl acetate
23. 23
    Sonstigeto give 0.63 gm

Vorschrift

A Grignard reagent is prepared using 4.79 gm. (0.024 mole) m-trifluoromethylbromobenzene, 0.59 gm. magnesium and 50 ml. tetrahydrofuran; to this is added 1.50 gm. (0.0071 mole) 4-cyano-4-dimethylaminocyclohexanone ethylene ketal (prepared in Example 41, Part B, dissolved in 40 ml. tetrahydrofuran. This reaction mixture is heated at the reflux temperature for 17 hours. It is then cooled, chilled in ice, and 20 ml. saturated aqueous ammonium chloride and benzene are added. The organic solution is then separated, initially washed with water, and then washed with brine. The solvents are then removed by evaporation under reduced pressure. The residue thus obtained is dissolved in diethyl ether, and 4 N ethereal hydrogen chloride is added until precipitation of the hydrochloride salt as a gum is complete. The supernatant liquid is decanted and the remaining gum is dissolved in methylene chloride. One N aqueous sodium hydroxide is added. The organic layer is then separated and the methylene chloride is removed by evaporation under reduced pressure. The residue thus obtained is transferred onto a 200 ml. column of silica gel and the chromatogram is developed with methylene chloride containing 3% methanol. The appropriate fractions, as determined by TLC, are collected and combined. The solvent is removed by evaporation under reduced pressure, and the gummy residue thus obtained is dissolved in diethyl ether. The ether solution is treated with 4 N ethereal hydrogen chloride until precipitation of the hydrochloride salt is complete. The precipitate is collected on a filter and then recrystallized from a mixture of methylene chloride and ethyl acetate to give 0.63 gm. (24% yield) of 4-(m-trifluoromethylphenyl)-4-dimethylaminocyclohexanone ethylene ketal hydrochloride having a melting point at 231° to 232° C.

Quelle