2-Methylindole → 2-(1H-indol-2-ylmethyl)-1,1,1-trifluoro-4-(4-fluorophenyl)-4-methylpentan-2-ol

HRID 2080576Notes

Reaction equation

HRID 2080576 reaction equation
[CH3:1][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[CH:6][CH:5]=2.C([Li])CCC.CC(C)([O-])C.[K+].[F:22][C:23]([F:38])([F:37])[C:24](=[O:36])[CH2:25][C:26]([C:29]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=1)([CH3:28])[CH3:27]>C(OCC)C>[NH:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH:10]=[C:2]1[CH2:1][C:24]([OH:36])([CH2:25][C:26]([C:29]1[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=1)([CH3:28])[CH3:27])[C:23]([F:22])([F:38])[F:37]

Participants

6

Reactant 4

HCID 72242-MethylindoleHCID 220326931,1,1-Trifluoro-4-(4-fluorophenyl)-4-methylpentan-2-oneHCID 23665647Potassium tert-butoxideHCID 178418339Butyllithium

Product 1

HCID 101264152-(1H-indol-2-ylmethyl)-1,1,1-trifluoro-4-(4-fluorophenyl)-4-methylpentan-2-olYield 26.2%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a diethyl ether solution of 53 mg of 2-methylindole was added 3 equivalents of n-butyl lithium followed by 90 mg of potassium tert-butoxide (t-BuOK) (solid) at room temperature. The mixture was allowed to stir for 30 minutes. 1,1,1-Trifluoro-4-(4-fluorophenyl)-4-methylpentan-2-one (100 mg) in diethyl ether was then added to the above mixture. The reaction was stirred at room for 1 hour. The reaction was quenched with saturated aqueous ammonium chloride, and extracted three times with EtOAc. The combined organic layers were washed with water, brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography to yield 40 mg of the title compound as a foam. Resolution to the (+)- and (−) enantiomers was accomplished by chiral HPLC on a CHIRALCEL® OD™ column, eluting with 10% isopropanol-hexanes.

Workup

  1. stirringThe reaction was stirred at room for 1 hour
  2. customThe reaction was quenched with saturated aqueous ammonium chloride
  3. extractionextracted three times with EtOAc
  4. washThe combined organic layers were washed with water, brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-f7821144e7aa4d83b4778fe7ee7dd3fb
Source dataset
uspto-grants-2011_04
Patent number
US07932392B2

Reaction notes

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