反应详情

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.

1. temperaturecooled condenser
2. customThe resulting reaction mixture
3. temperatureheated gently until a reaction
4. customTo the stirred reaction mixture
5. temperaturethat gentle reflux
6. temperatureis maintained
7. stirringThe reaction mixture is stirred for an additional two hours
8. temperatureThe resulting solution is then cooled to 0°
9. customthe reaction flask is fitted with
10. customtopped by a dry ice condenser
11. additionare added
12. additionis added dropwise to the stirred solution which
13. temperatureis cooled to 0° to -10° with an ice-acetone bath
14. temperatureto warm to 20°-25°
15. stirringstirring
16. temperatureThe solution is cooled to 0°
17. customto obtain an acidic solution to which
18. washThe resulting ether layer is washed with water
19. washwashed with a 5% sodium bicarbonate solution
20. dry with materialdried with anhydrous magnesium sulfate
21. filtrationfiltered
22. customevaporated at reduced pressure
23. customto yield a residual solid which
24. customis recrystallized from chlorobutane