Chlorotrimethylsilane → 1-(1-Methyl-1H-indol-3-yl)-3-(4-pyridyl)-3-trimethylsilyloxypropan-1-one

HRID 1599463Notes

Reaction equation

HRID 1599463 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[C:13]([C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[N:18]([CH3:25])[CH:17]=1)(=[O:15])[CH3:14].[N:26]1[CH:31]=[CH:30][C:29]([CH:32]=[O:33])=[CH:28][CH:27]=1.Cl[Si:35]([CH3:38])([CH3:37])[CH3:36]>C1COCC1>[CH3:25][N:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:16]([C:13](=[O:15])[CH2:14][CH:32]([C:29]2[CH:30]=[CH:31][N:26]=[CH:27][CH:28]=2)[O:33][Si:35]([CH3:38])([CH3:37])[CH3:36])=[CH:17]1

Participants

7

Reactant 5

HCID 6397ChlorotrimethylsilaneHCID 7912DiisopropylamineHCID 133894-PyridinecarboxaldehydeHCID 5941561-(1-Methyl-1H-indol-3-yl)ethanoneHCID 178418339Butyllithium

Product 1

HCID 232995901-(1-Methyl-1H-indol-3-yl)-3-(4-pyridyl)-3-trimethylsilyloxypropan-1-oneYield 51%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

1.6M n-Butyllithium (1.19 ml, 1.90 mmol) was added to dry THF (10 ml) containing. diisopropylamine (0.266 ml, 1.90 mmol) under Ar at 0° C. After 15 mins, the mixture was cooled to -78° C., and 3-acetyl-1-methyl-1H-indole (0.300 g, 1.73 mmol) in dry THF (5 ml) was added slowly. The resulting mixture was left at -78° C. for 1 h, before pyridine-4-carboxaldehyde (0.165 ml, 1.73 mmol) was added. The reaction mixture was then left at -78° C. for 1 h, before being allowed to warm to 0° C., whereupon chlorotrimethylsilane (0.439 ml, 3.46 mmol) was added. The mixture was then allowed to warm to room temp and stirred for 1 h, before being evaporated under reduced pressure and partitioned between dichloromethane and water. The organic layer was then dried (Na2SO4) and evaporated under reduced pressure to give a pale yellow solid which was purified by silica-gel chromatography (EtOAc as eluant) to give the title compound as a yellow solid (0.300 g, 51%).

Workup

  1. additioncontaining
  2. customat 0° C
  3. additionwas added
  4. waitThe reaction mixture was then left at -78° C. for 1 h
  5. additionwas added
  6. temperatureto warm to room temp
  7. custombefore being evaporated under reduced pressure
  8. custompartitioned between dichloromethane and water
  9. dry with materialThe organic layer was then dried (Na2SO4)
  10. customevaporated under reduced pressure
  11. customto give a pale yellow solid which
  12. customwas purified by silica-gel chromatography (EtOAc as eluant)

Sources & evidence

ORD record
ord-875e84876fcc41e4bf4bf3aa99a0d969
Source dataset
uspto-grants-1998_04
Patent number
US05741801

Reaction notes

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