Réaction #666568

Équation de réaction

3-hydroxy-3-methylbutyl toluene-4-sulfonate

potassium carbonate

(9R)-4-chloro-9-(trifluoromethyl)-9H-fluorene-2,9-diol

3-hydroxy-3-methylbutyl toluene-4-sulfonate

water

→

title compound

Rendement 69.3%

(9R)-4-Chloro-2-(3-hydroxy-3-methylbutyloxy)-9-(trifluoromethyl)-9H-fluoren-9-ol

Rendement 69.3%

Solvants

N,N-dimethylformamide

N,N-dimethylformamide

Conditions de réaction

Traitement

1. 1
   workup.STIRRINGthe mixture was further stirred at the same temperature for 9.5 hr
2. 2
   Températurecooled
3. 3
   Extractionthe mixture was extracted with ethyl acetate (900 ml)
4. 4
   LavageThe obtained organic layer was washed with water (500 ml, 3 times) and saturated brine (500 ml)
5. 5
   SéchageThe obtained organic layer was dried over anhydrous sodium sulfate
6. 6
   Filtrationthe insoluble material was filtered off
7. 7
   Autrethe solvent in the filtrate was evaporated
8. 8
   AutreThe obtained residue was purified by silica gel column chromatography (
9. 9
   workup.ADDITIONa mixture of hexane and ethyl acetate
10. 10
    Lavagefirst eluted with a mixture of (hexane:ethyl acetate) at a mixing ratio 3:1

Mode opératoire

Under a nitrogen atmosphere, (9R)-4-chloro-9-(trifluoromethyl)-9H-fluorene-2,9-diol (55.5 g) was dissolved in N,N-dimethylformamide (550 ml), 3-hydroxy-3-methylbutyl toluene-4-sulfonate (49.6 g) and potassium carbonate (39.5 g) were added, and the mixture was stirred at an oil bath temperature of 70° C. overnight. To the reaction mixture was added a solution of 3-hydroxy-3-methylbutyl toluene-4-sulfonate (4.0 g) in N,N-dimethylformamide (5 ml), and the mixture was further stirred at the same temperature for 9.5 hr. The reaction mixture was ice-cooled, water (800 ml) was added, and the mixture was extracted with ethyl acetate (900 ml). The obtained organic layer was washed with water (500 ml, 3 times) and saturated brine (500 ml). The obtained organic layer was dried over anhydrous sodium sulfate, the insoluble material was filtered off, and the solvent in the filtrate was evaporated. The obtained residue was purified by silica gel column chromatography (a mixture of hexane and ethyl acetate was used as an elution solvent, first eluted with a mixture of (hexane:ethyl acetate) at a mixing ratio 3:1, and then with the mixture at a mixing ratio 2:1, and further with the mixture at a mixing ratio 3:2) to give the title compound (49.5 g).

Source