Water → (9R)-4-Chloro-2-(3-hydroxy-3-methylbutoxy)-9-(trifluoromethyl)-9H-fluoren-9-ol

HRID 579386Notes

Reaction equation

HRID 579386 reaction equation
[Cl:1][C:2]1[C:14]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C@@:7]([C:16]([F:19])([F:18])[F:17])([OH:15])[C:6]=2[CH:5]=[C:4]([OH:20])[CH:3]=1.C1(C)C=CC(S(O[CH2:31][CH2:32][C:33]([OH:36])([CH3:35])[CH3:34])(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[Cl:1][C:2]1[C:14]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C@@:7]([C:16]([F:18])([F:19])[F:17])([OH:15])[C:6]=2[CH:5]=[C:4]([O:20][CH2:31][CH2:32][C:33]([OH:36])([CH3:35])[CH3:34])[CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 140012952-Methyl-4-[(4-methylbenzenesulfonyl)oxy]butan-2-ol2×HCID 117599289(9R)-4-Chloro-9-(trifluoromethyl)-9H-fluorene-2,9-diol

Product 1

HCID 117599101(9R)-4-Chloro-2-(3-hydroxy-3-methylbutoxy)-9-(trifluoromethyl)-9H-fluoren-9-olYield 69.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
70 °C

Procedure

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).

Workup

  1. stirringthe mixture was further stirred at the same temperature for 9.5 hr
  2. temperaturecooled
  3. extractionthe mixture was extracted with ethyl acetate (900 ml)
  4. washThe obtained organic layer was washed with water (500 ml, 3 times) and saturated brine (500 ml)
  5. dry with materialThe obtained organic layer was dried over anhydrous sodium sulfate
  6. filtrationthe insoluble material was filtered off
  7. customthe solvent in the filtrate was evaporated
  8. customThe obtained residue was purified by silica gel column chromatography (
  9. additiona mixture of hexane and ethyl acetate
  10. washfirst eluted with a mixture of (hexane:ethyl acetate) at a mixing ratio 3:1

Sources & evidence

ORD record
ord-60f6f79bf81c456a926931f55abfcff4
Source dataset
uspto-grants-2015_05
Patent number
US09040717B2

Reaction notes

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