反应详情

Sodium borohydride (0.37 g, 9.78 mmol) was added to a 0° C. solution of 4-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carbaldehyde (1.70 g, 6.52 mmol) in methanol (26 ml). Gas evolution was observed and the reaction mixture was stirred at RT for 30 mins and evaporated. Sat'd NaHCO3 and CH2Cl2 were added to the residue and the aqueous layer was extracted with CH2Cl2 (4×20 mL). The combined organic phase was dried (Na2SO4), filtered and evaporated to give [4-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazol-5-yl]methanol as a light yellow oil. A solution of this alcohol, imidazole (0.89 g, 13.0 mmol) and TBSCI (1.47 g, 9.78 mmol) in CH2Cl2 (22 mL) was stirred at RT overnight. Sat'd NaHCO3 was added and the aqueous layer was extracted with CH2Cl2 (2×20 mL). The combined organic phase was dried (Na2SO4), filtered, evaporated and purified by silica gel chromatography (0-35% EtOAc/hexanes) to give the title compound (2.19 g, 89%) as a clear oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.44 (s, 1H), 5.35 (s, 2H), 4.72 (s, 2H), 3.51 (t, J=8.2 Hz, 2H), 0.90-0.96 (m, 2H), 0.89 (s, 9H), 0.09 (s, 6H), 0.00 (s, 9H).

1. customevaporated
2. additionSat'd NaHCO3 and CH2Cl2 were added to the residue
3. extractionthe aqueous layer was extracted with CH2Cl2 (4×20 mL)
4. dry with materialThe combined organic phase was dried (Na2SO4)
5. filtrationfiltered
6. customevaporated