Sodium hydride → 4-Bromo-1-(triisopropylsilyl)-7-azaindole

HRID 408160Notes

Reaction equation

HRID 408160 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:9]=[CH:8][N:7]=[C:6]2[NH:10][CH:11]=[CH:12][C:5]=12.Cl[Si:14]([CH:21]([CH3:23])[CH3:22])([CH:18]([CH3:20])[CH3:19])[CH:15]([CH3:17])[CH3:16]>C1COCC1>[Br:3][C:4]1[CH:9]=[CH:8][N:7]=[C:6]2[N:10]([Si:14]([CH:21]([CH3:23])[CH3:22])([CH:18]([CH3:20])[CH3:19])[CH:15]([CH3:17])[CH3:16])[CH:11]=[CH:12][C:5]=12

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 139400Triisopropylsilyl chlorideHCID 222736434-Bromo-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 114736554-Bromo-1-(triisopropylsilyl)-7-azaindoleYield 84.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (8.37 g, 209 mmol; 60% oil dispersion) was slowly added to 4-bromo-1H-pyrrolo[2,3-b]pyridine (33.0 g, 167 mmol) in THF (500 mL) at 0° C. The reaction was stirred for 15 minutes. Chlorotriisopropylsilane (38.7 g, 201 mmol) was then added in one portion. The suspension was warmed to room temperature and stirred for 30 minutes. The suspension was then cooled to about 0-5° C. and quenched with saturated aqueous NH4Cl (about 200 mL). The aqueous phase was extracted with hexanes (3×300 mL), and the combined organic phases were dried (MgSO4) and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with hexanes to yield 4-bromo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (50 g, 84% yield) as an oil, which solidified upon standing. 1H NMR (400 MHz, CDCl3) δ 8.05 (d, 1H), 7.34 (d, 1H), 7.22 (d, Hz, 2H), 6.59 (d, 1H), 1.88-1.80 (m, 3H), 1.11 (d, 18H).

Workup

  1. stirringstirred for 30 minutes
  2. temperatureThe suspension was then cooled to about 0-5° C.
  3. customquenched with saturated aqueous NH4Cl (about 200 mL)
  4. extractionThe aqueous phase was extracted with hexanes (3×300 mL)
  5. dry with materialthe combined organic phases were dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica gel eluting with hexanes

Sources & evidence

ORD record
ord-585fcdd4830e4d1fb5348d830250c13a
Source dataset
uspto-grants-2014_06
Patent number
US08758830B2

Reaction notes

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