반응 #549484

반응 방정식

ammonium chloride

magnesium

4-cyano-4-dimethylaminocyclohexanone ethylene ketal

hydrogen chloride

m-trifluoromethylbromobenzene

hydrogen chloride

→

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

수율 24.0%

용매

diethyl ether

benzene

diethyl ether

tetrahydrofuran

tetrahydrofuran

ether

methylene chloride

반응 조건

후처리

1. 1
   workup.ADDITIONto this is added 1.50 gm
2. 2
   workup.DISSOLUTIONdissolved in 40 ml
3. 3
   온도This reaction mixture is heated at the reflux temperature for 17 hours
4. 4
   온도It is then cooled
5. 5
   온도chilled in ice
6. 6
   기타The organic solution is then separated
7. 7
   세척initially washed with water
8. 8
   세척washed with brine
9. 9
   기타The solvents are then removed by evaporation under reduced pressure
10. 10
    기타The residue thus obtained
11. 11
    기타The 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
    기타The organic layer is then separated
15. 15
    기타the methylene chloride is removed by evaporation under reduced pressure
16. 16
    기타The residue thus obtained
17. 17
    기타are collected
18. 18
    기타The solvent is removed by evaporation under reduced pressure
19. 19
    기타the gummy residue thus obtained
20. 20
    기타The precipitate is collected on
21. 21
    여과a filter
22. 22
    기타recrystallized from a mixture of methylene chloride and ethyl acetate
23. 23
    기타to give 0.63 gm

실험 절차

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.

출처