2-(Chloromethoxy)ethyltrimethylsilane (stabilized with Diisopropylethylamine)

• 5-Bromoindole [B1738]
• Sodium Hydride (60%, dispersion in Paraffin Liquid) [S0481]
• 2-(Chloromethoxy)ethyltrimethylsilane (stabilized with Diisopropylethylamine) (= SEM-Cl) [C1339]
• DMF

Sodium hydride (49.0 mg, 1.22 mmol) in DMF (1 mL) was stirred at 0 °C for 5 minutes and 5-bromoindole (200 mg, 1.02 mmol) was added to the solution and stirred at 0 °C for 10 minutes. Then SEM-Cl (220 µL, 1.28 mmol) in DMF (0.5 mL) was added to the solution and stirred at 0 °C for 20 minutes. The reaction was quenched with water and the aqueous layer was extracted with ethyl acetate and washed with brine. The organic phase was dried over anhydrous sodium sulfate and filtered. The solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate:hexane = 0:100 - 5:95) to give 1 as a colorless oil (256 mg, 77% yield).

The reaction mixture was monitored by TLC (ethyl acetate:hexane = 1:9, Rf = 0.47).

5-Bromo-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indole (1)

¹H NMR (270 MHz, CDCl₃); δ 7.75 (d, J = 1.6 Hz, 1H), 7.38–7.32 (m, 2H), 7.16 (d, J = 3.2 Hz, 1H), 6.46 (d, J = 3.2 Hz, 1H), 5.45 (s, 2H), 3.47–3.41 (m, 2H), 0.90–0.84 (m, 2H), -0.07 (s, 9H).

• Protecting groups for the pyrrole and indole nitrogen atom. The [2-(trimethylsilyl)ethoxy]methyl moiety. Lithiation of 1-[[2-(trimethylsilyl)ethoxy]methyl]pyrrole
  • J. M. Muchowski, D. R. Solas, J. Org. Chem. 1984, 49, 203.