Water → Ethyl 4-[(9R)-4-chloro-9-hydroxy-9-(trifluoromethyl)-9H-fluoren-2-yloxy]butyrate

HRID 579393Notes

Reaction equation

HRID 579393 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.C(=O)([O-])[O-].[K+].[K+].Br[CH2:28][CH2:29][CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32].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]([OH:15])([C:16]([F:18])([F:19])[F:17])[C:6]=2[CH:5]=[C:4]([O:20][CH2:28][CH2:29][CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 76300Ethyl 4-bromobutyrateHCID 117599289(9R)-4-Chloro-9-(trifluoromethyl)-9H-fluorene-2,9-diol

Product 1

HCID 117599124Ethyl 4-[(9R)-4-chloro-9-hydroxy-9-(trifluoromethyl)-9H-fluoren-2-yloxy]butyrate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(9R)-4-Chloro-9-(trifluoromethyl)-9H-fluorene-2,9-diol (200 mg) obtained in step 10 of example 1 was dissolved in N,N-dimethylformamide (2 ml), potassium carbonate (185 mg) and ethyl 4-bromobutyrate (105 μl) were added, and the mixture was stirred at room temperature for 7 hr. To the reaction mixture was added water, and the mixture was extracted twice with ethyl acetate. The obtained organic layer was washed successively with water (twice) and saturated brine. The obtained organic layer was dried over anhydrous magnesium 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 at a mixing ratio 5:1 (hexane:ethyl acetate), then successively with a mixture at a mixing ratio 3:1, and further with a mixture at a mixing ratio 2:1) to give the title compound (197 mg).

Workup

  1. extractionthe mixture was extracted twice with ethyl acetate
  2. washThe obtained organic layer was washed successively with water (twice) and saturated brine
  3. dry with materialThe obtained organic layer was dried over anhydrous magnesium sulfate
  4. filtrationthe insoluble material was filtered off
  5. customthe solvent in the filtrate was evaporated
  6. customThe obtained residue was purified by silica gel column chromatography (
  7. additiona mixture of hexane and ethyl acetate
  8. washfirst eluted with a mixture at a mixing ratio 5:1 (hexane:ethyl acetate)

Sources & evidence

ORD record
ord-8992b4e1e933499ea15c34f79db96880
Source dataset
uspto-grants-2015_05
Patent number
US09040717B2

Reaction notes

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