反应详情

温度

60 °C

To a stirred solution of 2-hydroxymethylbenzimidazole (31.94, 0.216 mol) in dry DMF (450 mL) was added N,N-diisopropylethylamine (90 mL, 0.52 mol) followed by 2-(trimethylsily)ethoxymethyl chloride (75% in pentane, 55 g, 0.25 mol) and the mixture heated to 60° C. for 2 h. The mixture was cooled to room temperature, concentrated under reduced pressure and partitioned between EtOAc (400 mL) and distilled water (700 mL). The phases were separated and the aqueous layer extracted with EtOAc (2×200 mL). The combined organic extracts were washed with brine (1×400 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. Purification of the crude oil by column chromatography on silica gel (4% MeOH/CH2Cl2) afforded the desired 1-(2-trimethylsilylethoxymethyl)-2-hydroxymethylbenzimidazole (26.28 g, 44%) as a yellow oil. 1H NMR (CDCl3) δ −0.04 (s, 9H), 0.89 (t, 2H, J=9 Hz), 1.75 (br s, 1H), 3.55 (t, 2H, J=9 Hz), 4.94 (s, 2H), 7.26-7.30 (m, 2H), 7.43-7.45 (m, 1H), 7.70-7.72 (m, 1H).

1. temperatureThe mixture was cooled to room temperature
2. concentrationconcentrated under reduced pressure
3. custompartitioned between EtOAc (400 mL)
4. distillationdistilled water (700 mL)
5. customThe phases were separated
6. extractionthe aqueous layer extracted with EtOAc (2×200 mL)
7. washThe combined organic extracts were washed with brine (1×400 mL)
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customPurification of the crude oil by column chromatography on silica gel (4% MeOH/CH2Cl2)