Sodium hydride → 4-Chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo(2,3-b)pyridine

HRID 347558Notes

Reaction equation

HRID 347558 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][N:7]=[C:6]2[NH:10][CH:11]=[CH:12][C:5]=12.Cl[CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19]>CN(C=O)C>[Cl:3][C:4]1[CH:9]=[CH:8][N:7]=[C:6]2[N:10]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[CH:11]=[CH:12][C:5]=12

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 113894934-Chloro-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 116735894-Chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo(2,3-b)pyridineYield 53%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of NaH (88 mg, 60% in mineral oil, 2.2 mmol) in DMF (1 mL) was added 4-chloro-1H-pyrrolo[2,3-b]pyridine (305 mg, 2 mmol, prepared according to Thibault, C. et al. Org. Lett. 2003, 5, 5023) at room temperature with stirring. The mixture was stirred for 5 min and trimethylsilylethyl chloromethyl ether (350 mg, 2.1 mmol, Aldrich) was added. The mixture was stirred at room temperature for 1 h, poured onto ice, and extracted with ethyl acetate (3×10 mL). The combined extracts were washed with brine, dried (MgSO4) and concentrated under reduced pressure to give the crude product, which was purified by flash chromatograph (5% ethyl acetate in hexanes) to afford the title compound (300 mg, 1.06 mmol, 53%) as a liquid. 1H NMR (CDCl3) δ 8.28 (d, 1H, J=5.5 Hz), 7.45 (d, 1H, J=3.6 Hz), 7.18 (d, 1H, J=5.5 Hz), 6.69 (d, 1H, J=3.6 Hz), 5.74 (s, 2H), 3.60 (t, 2H, J=6.8 Hz), 0.96 (t, 2H, J=6.8 Hz), 0.07 (s, 9H); MS(ESI+) m/z 283 and 285 (M+H, 1 Cl)+.

Workup

  1. stirringThe mixture was stirred for 5 min
  2. stirringThe mixture was stirred at room temperature for 1 h
  3. additionpoured onto ice
  4. extractionextracted with ethyl acetate (3×10 mL)
  5. washThe combined extracts were washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. customto give the crude product, which
  9. customwas purified by flash chromatograph (5% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-06aa2a03d66742e585660ac982ea57a1
Source dataset
uspto-grants-2007_02
Patent number
US07173031B2

Reaction notes

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