Potassium hydride → 5-Bromo-3-(1-Methylpiperidin-4-yl)-1-Triisopropylsilylindole

HRID 277982Notes

Reaction equation

HRID 277982 reaction equation
[H-].[K+].[Br:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[C:7]2[CH:13]1[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]1.FC(F)(F)S(O[Si:26]([CH:33]([CH3:35])[CH3:34])([CH:30]([CH3:32])[CH3:31])[CH:27]([CH3:29])[CH3:28])(=O)=O>O1CCCC1>[Br:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([Si:26]([CH:33]([CH3:35])[CH3:34])([CH:30]([CH3:32])[CH3:31])[CH:27]([CH3:29])[CH3:28])[CH:8]=[C:7]2[CH:13]1[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]1

Participants

5

Reactant 3

HCID 82127Potassium hydrideHCID 2724529Triisopropylsilyl trifluoromethanesulfonateHCID 157453445-bromo-3-(1-methylpiperidin-4-yl)-1H-indole

Product 1

HCID 120859685-Bromo-3-(1-Methylpiperidin-4-yl)-1-TriisopropylsilylindoleYield 173.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a 10° C. slurry of potassium hydride (1.6 g, 14.3 mmol, 35% in mineral oil) in tetrahydrofuran (40 mL) was added neat 5-bromo-3-(1-methyl-4-piperidinyl)indole (2.8 g, 9.5 mmol) portionwise over 30 minutes. The resulting reaction mixture was stirred at 0° C. for 1 hour. Triisopropylsilyl trifluoromethanesulfonate (3.1 mL, 11.4 mmol) was added dropwise over 20 minutes and a slight exotherm was observed. After stirring 2 hours at 0° C., the reaction was quenched with ice chips then diluted with water and methylene chloride. The layers were separated and the aqueous layer was extracted with methylene chloride. The organic extracts were combined, washed with brine, dried over sodium sulfate, and concentrated in vacuo to give 7.4 g of a clear colorless oil. Purification by chromatography (florisil, 50:50 methylene chloride:hexanes, then 100% methylene chloride, then 95:5 methylene chloride:methanol) provided 3.6 g (84.1%) of the title compound. MS(FD) 448, 450 (M+).

Workup

  1. customThe resulting reaction mixture
  2. stirringAfter stirring 2 hours at 0° C.
  3. customthe reaction was quenched with ice chips
  4. additionthen diluted with water and methylene chloride
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with methylene chloride
  7. washwashed with brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e84510730f114cdc9d45f66906e36a7e
Source dataset
uspto-grants-2002_03
Patent number
US06358972B1

Reaction notes

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