HCID 59437226, compound → 1-[1-(2,2-Dimethyl-1,3-dioxolan-4-ylmethyl)-1H-indol-3-yl]-2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-benzotriazol-5-yl]ethanol

HRID 244475Notes

Reaction equation

HRID 244475 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.[CH3:23][C:24]1([CH3:45])[O:28][CH:27]([CH2:29][N:30]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:32]([C:39](=[O:44])[C:40]([F:43])([F:42])[F:41])=[CH:31]2)[CH2:26][O:25]1>C1COCC1>[CH3:23][C:24]1([CH3:45])[O:28][CH:27]([CH2:29][N:30]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:32]([C:39]([C:2]3[CH:17]=[CH:16][C:5]4[N:6]([C:9]5[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=5)[N:7]=[N:8][C:4]=4[CH:3]=3)([OH:44])[C:40]([F:43])([F:42])[F:41])=[CH:31]2)[CH2:26][O:25]1

Participants

5

Reactant 3

HCID 59437226HCID 59437226, compoundHCID 594372891-[1-(2,2-dimethyl-1,3-dioxolan-4-ylmethyl)-1H-indol-3-yl]-2,2,2-trifluoroethanoneHCID 178418339Butyllithium

Product 1

HCID 594372331-[1-(2,2-Dimethyl-1,3-dioxolan-4-ylmethyl)-1H-indol-3-yl]-2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-benzotriazol-5-yl]ethanolYield 55.5%

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 (0.22 mL of a 2.5 M solution in hexanes, 0.55 mmol). After 1 minute, a chilled (−78° C.) solution of 1-[1-(2,2-dimethyl-1,3-dioxolan-4-ylmethyl)-1H-indol-3-yl]-2,2,2-trifluoroethanone (185 mg, 0.57 mmol) in 1 mL of THF was added. After 30 minutes, the mixture was quenched with brine solution (50 mL) and extracted with ethyl acetate. The combined organic layers were washed with water, dried over anhydrous sodium sulfate, and solvent evaporated in vacuo to afford a yellow oil. The residue was purified by column chromatography over silica gel eluting with 0-60% ethyl acetate in hexanes and fractions corresponding to MS m/z 541 (MH+) peak were pooled and concentrated in vacuo to afford 150 mg of the title compound as a brownish solid.

Workup

  1. additionwas added
  2. waitAfter 30 minutes
  3. customthe mixture was quenched with brine solution (50 mL)
  4. extractionextracted with ethyl acetate
  5. washThe combined organic layers were washed with water
  6. dry with materialdried over anhydrous sodium sulfate, and solvent
  7. customevaporated in vacuo
  8. customto afford a yellow oil
  9. customThe residue was purified by column chromatography over silica gel eluting with 0-60% ethyl acetate in hexanes and fractions corresponding to MS m/z 541 (MH+) peak
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d7a80266c1f64016a2a106d2eb53ce7c
Source dataset
uspto-grants-2014_02
Patent number
US08658637B2

Reaction notes

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