Methanol → Benzimidazole

Participants

Reaction Steps

2-Chloro-1-(β-D-ribofuranosyl)-1H-benzimidazole (0.5 g) was suspended in pyridine (8.8 mL). To the stirred mixture was added dropwise 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane (0.59 mL) under ice-cooling, and the mixture was stirred at room temperature for 26 hours. To the reaction mixture was added methanol (2 mL), and the mixture was concentrated under reduced pressure. To the obtained residue was added water, and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with 1 mol/L hydrochloric acid, a saturated aqueous sodium hydrogen carbonate solution and brine successively and dried over anhydrous magnesium sulfate. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by column chromatography on silica gel (ethyl acetate/hexane=2/9) to give 2-chloro-1-[3,5-O,O-1,1,3,3-tetra-isopropyldisiloxanyl)-β-D-ribofuranosyl]-1H-benzimidazole (0.35 g). The obtained compound (0.34 g), triethylamine (0.12 mL) and 4-dimethylaminopyridine (0.08 g) were dissolved in dichloromethane (13 mL), and to the stirred mixture was added dropwise trifluoromethanesulfonylchloride (0.09 mL) under ice-cooling. The mixture was stirred at room temperature for 1 hour. To the reaction mixture was added a saturated aqueous sodium hydrogen carbonate solution (10 mL), and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The filtrate was concentrated under reduced pressure, and the obtained residue was dissolved in N,N-dimethylformamide (3 mL). To the mixture was cesium acetate (0.17 g), and the mixture was stirred at 30° C. for 15 hours. To the reaction mixture was added water (10 mL), and the resulting mixture was extracted with diethyl ether. The organic layer was washed with water and brine successively and dried over anhydrous magnesium sulfate. The filtrate was concentrated under reduced pressure, and the obtained residue was dissolved in tetrahydrofuran (3.9 mL). To the stirred mixture was added dropwise 1 mol/L tetrabutylammonium fluoride-tetrahydrofuran solution (1.47 mL) under ice-cooling. The mixture was stirred under ice-cooling for 1 hour. To the reaction mixture was added acetic acid (0.08 mL), and the mixture was concentrated under reduced pressure. The obtained residue was purified by column chromatography on silica gel (ethylacetate/hexane=4/1) to give 1-(2-O-acetyl-β-D-arabinofuranosyl)-2-chloro-1H-benzimidazole (0.12 g). The obtained compound (0.12 g), 4-phenylbenzylamine (0.26 g) and N,N-diisopropylethylamine (0.37 mL) were suspended in n-propanol (3.6 mL), and the mixture was refluxed for 43 hours. The reaction mixture was concentrated under reduced pressure, and the obtained residue was purified by column chromatography on aminopropylated silica gel (dichloromethane/methanol=12/1) to give the title compound (0.15 g).

Provenance & Evidence