Reaktion #4845

Reaktionsgleichung

3-bromo-1-methoxybenzene

1,2-dibromoethane

3-bromo-1-methoxybenzene

hexafluoroacetone

hexafluoroacetone

hexafluoroacetone

hydrochloric acid

magnesium

→

1-methoxy-3-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]benzene

Lösungsmittel

water

ether

tetrahydrofuran

water

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturcooled condenser
2. 2
   SonstigeThe resulting reaction mixture
3. 3
   Temperaturheated gently until a reaction
4. 4
   SonstigeTo the stirred reaction mixture
5. 5
   Temperaturthat gentle reflux
6. 6
   Temperaturis maintained
7. 7
   workup.STIRRINGThe reaction mixture is stirred for an additional two hours
8. 8
   TemperaturThe resulting solution is then cooled to 0°
9. 9
   Sonstigethe reaction flask is fitted with
10. 10
    Sonstigetopped by a dry ice condenser
11. 11
    workup.ADDITIONare added
12. 12
    workup.ADDITIONis added dropwise to the stirred solution which
13. 13
    Temperaturis cooled to 0° to -10° with an ice-acetone bath
14. 14
    Temperaturto warm to 20°-25°
15. 15
    workup.STIRRINGstirring
16. 16
    TemperaturThe solution is cooled to 0°
17. 17
    Sonstigeto obtain an acidic solution to which
18. 18
    WaschenThe resulting ether layer is washed with water
19. 19
    Waschenwashed with a 5% sodium bicarbonate solution
20. 20
    Trocknendried with anhydrous magnesium sulfate
21. 21
    Filtrationfiltered
22. 22
    Sonstigeevaporated at reduced pressure
23. 23
    Sonstigeto yield a residual solid which
24. 24
    Sonstigeis recrystallized from chlorobutane

Vorschrift

To a suspension of 13.5 g (0.55 g atoms) of sublimed magnesium chips in 25 ml of anhydrous tetrahydrofuran in a reaction flask fitted with a water-cooled condenser are added 10 g (0.05 mole) of 3-bromo-1-methoxybenzene and 0.5 ml of 1,2-dibromoethane. The resulting reaction mixture is stirred and heated gently until a reaction is initiated. To the stirred reaction mixture is added dropwise a solution of 90 g (0.48 mole) of 3-bromo-1-methoxybenzene in 250 ml of anhydrous tetrahydrofuran at such a rate that gentle reflux is maintained. The reaction mixture is stirred for an additional two hours. The resulting solution is then cooled to 0° and the reaction flask is fitted with a jacketed dropping funnel topped by a dry ice condenser. The water condenser is replaced by an additional dry ice condenser. To the jacketed dropping funnel are added 85 g (50 ml) (0.55 mole) of condensed hexafluoroacetone. The condensed hexafluoroacetone is added dropwise to the stirred solution which is cooled to 0° to -10° with an ice-acetone bath. When the addition of the hexafluoroacetone is complete, the resulting solution is allowed to warm to 20°-25° and stirring is continued for an additional 18 hours. The solution is cooled to 0° and treated with 6N hydrochloric acid to obtain an acidic solution to which is added 1-liter of ether. The resulting ether layer is washed with water, washed with a 5% sodium bicarbonate solution, dried with anhydrous magnesium sulfate, filtered and evaporated at reduced pressure to yield a residual solid which is recrystallized from chlorobutane to give 78 g of 1-methoxy-3-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]benzene.

Quelle