Reaction #7226

Reaction equation

2-chloromethylbenzimidazole

N,N-diisopropylethylamine

2-(trimethylsilyl)ethoxymethyl chloride

→

title compound

Yield 67.7%

2-Chloromethyl-1-(2-trimethylsilylethoxymethyl)-1H-benzimidazole

Yield 67.7%

Solvents

THF

Conditions

Workup

1. 1
   Otherwas removed in vacuo
2. 2
   Washwashed with water (100 mL) and brine (100 mL)
3. 3
   DryingThe organic layer was dried over sodium sulfate
4. 4
   Filtrationfiltered
5. 5
   Concentrationconcentrated in vacuo
6. 6
   Otherto afford the crude product as a yellow oil
7. 7
   OtherPurification by flash chromatography (silica gel, 100:2:1 CH2Cl2-methanol-ammonium hydroxide)

Procedure

To a stirred solution of 2-chloromethylbenzimidazole (1.89 g, 11.4 mmol) in dry THF (57 mL) was added N,N-diisopropylethylamine (3.00 mL, 17.2 mmol) and 2-(trimethylsilyl)ethoxymethyl chloride (1.90 mL, 10.8 mmol) both via syringe under nitrogen at room temperature. The mixture was stirred for 3 days at which time the solvent was removed in vacuo. The residue was taken up in CH2Cl2 (100 mL) and washed with water (100 mL) and brine (100 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to afford the crude product as a yellow oil. Purification by flash chromatography (silica gel, 100:2:1 CH2Cl2-methanol-ammonium hydroxide) provided 2.17 g (65%) of the title compound as a yellow oil, which solidified on standing. 1H NMR (CDCl3) δ−0.06 (s, 9H), 0.92 (t, 2H, J=7.5 Hz), 3.57 (t, 2H, J=7.5 Hz), 4.91 (s, 2H), 5.65 (s, 2H), 7.31–7.36 (m, 2H), 7.50 (d, 1H, J=7.5 Hz), 7.78 (d, 1H, J=7.5 Hz).

Source