反应详情

温度

0 °C

To a solution of methyl 2-[(2,4-dichlorophenyl)amino]-1-(3-hydroxypropyl)-1H-benzimidazole-7-carboxylate (Reference Example 103; 72.0 g, 0.183 mol) in tetrahydrofuran (800 mL) and triethylamine (127 mL) was added methanesulfonyl chloride (42.5 mL, 0.731 mol) at 0° C. The mixture was stirred at 0° C. for 2 hr, and diluted with aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The mixture of the residue, potassium carbonate (75.9 g, 0.549 mol) in N,N-dimethylformamide (800 mL) was stirred at 70° C. for 3 h. The mixture was diluted with water, and the precipitate was collected by filtration, washed with water, washed with diisopropyl ether to give the solid, which was recrystallized from ethanol/ethyl acetate to give the title compound as a colorless crystal (50.2 g, 0.133 mol, 73% in 2 steps).

1. extractionextracted with ethyl acetate
2. washThe combined organic layer was washed with brine
3. dry with materialdried over anhydrous magnesium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. stirringwas stirred at 70° C. for 3 h
7. filtrationthe precipitate was collected by filtration
8. washwashed with water
9. washwashed with diisopropyl ether
10. customto give the solid, which
11. customwas recrystallized from ethanol/ethyl acetate