Sodium hydride → Methyl 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-4-carboxylate

Participants

Reaction Steps

To a stirred suspension of sodium hydride (572 mg, 23.8 mmol, 94%) in dry DMF (50 mL) at 0° C. was added methyl 1H-imidazole-4-carboxylate (3.0 g, 23.8 mmol) in DMF (90 mL) and was allowed to warm up to room temperature over 30 min. The reaction mixture was cooled to 0° C. and was treated dropwise with (2-(chloromethoxy)ethyl)trimethylsilane (Aldrich, 4.77 g, 28.6 mmol). The cold bath was removed and the mixture was stirred for 16 h. The reaction mixture was quenched by the addition of ice-flakes and then by water, and extracted with EtOAc (3×). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo to give crude product. The crude material was purified by flash chromatography (gradient from 2 to 5% MeOH/CH2Cl2) to provide the title compound (4.46 g, 73%). 1H NMR (CDCl3) δ 7.72 (s, 1H), 7.61 (s, 1H), 5.29 (s, 2H), 3.90 (s, 3H), 3.49 (t, J=8.0 Hz, 2H), 0.90 (t, J=8.0 Hz, 2H), 0.01 (s, 9H); MS(ESI+) m/z 257.2 (M+H)+.

Provenance & Evidence