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

HRID 1070983ノート

反応式

HRID 1070983 の反応式
[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]

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-20 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-04134bba6ec347c1aa521f1d2ba3249e
出典データセット
uspto-grants-2005_06
特許番号
US06903215B2

反応ノート

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