1-Methyl-3-(trifluoroacetyl)-1H-indole → 2,2,2-Trifluoro-1-[1-(4-fluorophenyl)-1H-benzotriazol-5-yl]-1-(1-methyl-1H-indol-3-yl)ethanol

HRID 244473

Reaction equation

HRID 244473 reaction equation
Br[C:2]1[CH:17]=[CH:16][C:5]2[N:6]([C:9]3[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=3)[N:7]=[N:8][C:4]=2[CH:3]=1.C([Li])CCC.[F:23][C:24]([F:38])([F:37])[C:25]([C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[N:29]([CH3:36])[CH:28]=1)=[O:26]>C1COCC1>[F:38][C:24]([F:23])([F:37])[C:25]([C:2]1[CH:17]=[CH:16][C:5]2[N:6]([C:9]3[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=3)[N:7]=[N:8][C:4]=2[CH:3]=1)([C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[N:29]([CH3:36])[CH:28]=1)[OH:26]

Participants

5

Reactant 3

HCID 35243881-Methyl-3-(trifluoroacetyl)-1H-indoleHCID 59437226HCID 59437226, compoundHCID 178418339Butyllithium

Product 1

HCID 594372652,2,2-Trifluoro-1-[1-(4-fluorophenyl)-1H-benzotriazol-5-yl]-1-(1-methyl-1H-indol-3-yl)ethanolYield 18.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a chilled (−78° C.) solution of 5-bromo-1-(4-fluorophenyl)-1H-benzotriazole (145 mg, 0.5 mmol) in anhydrous THF (3 mL) was added n-butyllithium (0.25 mL of a 2.5 M solution in hexanes, 0.625 mmol) over a 1 minute period followed by a chilled (−78° C.) solution of 2,2,2-trifluoro-1-(1-methyl-1H-indol-3-yl)ethanone (170 mg, 0.75 mmol) in 1 mL of THF. After 15 minutes, the mixture quenched with brine (50 mL) and extracted with three 50 mL portions of methylene chloride. The combined organic layers were washed with water, dried over anhydrous sodium sulfate and concentrated in vacuo to afford a yellow oil. The residue was purified by column chromatography over silica gel eluting with 0-50% ethyl acetate in hexanes to afford 40 mg of the title compound as a light yellow solid. MS m/z 441 (MH+).

Workup

  1. customthe mixture quenched with brine (50 mL)
  2. extractionextracted with three 50 mL portions of methylene chloride
  3. washThe combined organic layers were washed with water
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customto afford a yellow oil
  7. customThe residue was purified by column chromatography over silica gel eluting with 0-50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-426926191af74a77ab904f5a571fc39b
Source dataset
uspto-grants-2014_02
Patent number
US08658637B2

Linked notes

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