2-Methylindole → 1,1,1-trifluoro-2-(1H-indol-2-ylmethyl)-4-methyl-4-pyridin-2-ylpentan-2-ol

HRID 2080585Notes

Reaction equation

HRID 2080585 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:37])([F:36])[C:24](=[O:35])[CH2:25][C:26]([CH3:34])([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=1)[CH3:27]>C1COCC1>[F:37][C:23]([F:22])([F:36])[C:24]([CH2:1][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[CH:6][CH:5]=2)([OH:35])[CH2:25][C:26]([CH3:27])([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=1)[CH3:34]

Participants

6

Reactant 4

HCID 72242-MethylindoleHCID 223984871,1,1-Trifluoro-4-methyl-4-pyridin-2-ylpentan-2-oneHCID 23665647Potassium tert-butoxideHCID 178418339Butyllithium

Product 1

HCID 102371281,1,1-trifluoro-2-(1H-indol-2-ylmethyl)-4-methyl-4-pyridin-2-ylpentan-2-olYield 28.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

To a solution of 42.4 mg (0.324 mmol, 1.5 eq.) of 2-methylindole in 2 mL of THF, 389 μL (0.972 mmol, 4.5 eq.) of n-butyl lithium (2.5 M solution in hexanes) and 648 μL (0.648 mmol, 3.0 eq.) of potassium tert-butoxide (1.0 M solution in THF) were added dropwise at −75° C. The resulting mixture was allowed to warm to −20° C. over 30 minutes. The reaction mixture was cooled to −75° C. and a solution of 50 mg (0.216 mmol) of 1,1,1-trifluoro-4-methyl-4-pyridin-2-ylpentan-2-one in 1 mL of THF was added at this temperature. The resulting mixture was stirred at this temperature for 30 minutes and then quenched with saturated NH4Cl solution. The product was extracted into ether and the ethereal layer was washed with water and brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography to give 22 mg (28%) of the title compound as a white foam.

Workup

  1. temperatureThe reaction mixture was cooled to −75° C.
  2. customquenched with saturated NH4Cl solution
  3. extractionThe product was extracted into ether
  4. washthe ethereal layer was washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-5c2d0da0296a4b59bb403a9b2c4a6e78
Source dataset
uspto-grants-2011_04
Patent number
US07932392B2

Reaction notes

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