3-(Trifluoroacetyl)indole → 2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-(1H-indol-3-yl)ethanol

HRID 244423Notes

Reaction equation

HRID 244423 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)[N:6]=[CH:5]2.C([Li])CCC.[F:23][C:24]([F:37])([F:36])[C:25]([C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[NH:29][CH:28]=1)=[O:26]>C1COCC1.CCCCCC>[F:37][C:24]([F:23])([F:36])[C:25]([C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)[N:6]=[CH:5]2)([C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[NH:29][CH:28]=1)[OH:26]

Participants

6

Reactant 3

HCID 5891263-(Trifluoroacetyl)indoleHCID 468307945-bromo-1-(4-fluorophenyl)-1H-indazoleHCID 178418339Butyllithium

Product 1

HCID 579433222,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-(1H-indol-3-yl)ethanolYield 49%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a chilled (−78° C.) solution of 2.67 g (9.20 mmol) 5-bromo-1-(4-fluorophenyl)-1H-indazole in 10 mL of anhydrous THF was added 7.36 mL (18.40 mmol) of a 2.5 M solution of n-butyllithium in hexane followed by a solution of 1.00 g (4.69 mmol) of 2,2,2-trifluoro-1-(1H-indol-3-yl)ethanone in 5 mL of THF in one portion. The reaction was then stirred at −78° C. for 30 minutes and quenched with 5 mL of water. The mixture was warmed to room temperature and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography (20%-40% ethyl acetate in hexanes). The major fractions were combined and concentrated to afford 978 mg of 2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-(1H-indol-3-yl)ethanol. MS m/z 426.39 (MIT).

Workup

  1. customquenched with 5 mL of water
  2. temperatureThe mixture was warmed to room temperature
  3. extractionextracted with ethyl acetate
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography (20%-40% ethyl acetate in hexanes)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-deab3d3550bc40adaa532cbc0ce8ff48
Source dataset
uspto-grants-2014_02
Patent number
US08658637B2

Reaction notes

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