反应详情

Combine (1H-benzimidazol-2-yl)(1-ethoxycarbonylpiperidin-4-yl)amine (1.5 g, 5.2 mmol) and tetrahydrofuran (45 mL) and dimethylformamide (5 mL). Cool in an ice bath. Add sodium hydride (0.25 g, 60% in oil, 6.24 mmol). Warm to ambient temperature. After about 90 minutes, when the gas evolution ceases, add 2-(chloromethyl)furan (1.04 g, 8.5 mmol). After 56 hours, add ice and then a saturated aqueous solution of ammonium chloride. Evaporate the reaction mixture to remove most of the tetrahydrofuran, dilute with ethyl acetate and extract with a saturated aqueous sodium bicarbonate solution, water, and then brine. Dry the organic layer over MgSO4, filter and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with ethyl acetate to give (1-(fur-2-ylmethyl)-1H-benzimidazol-2-yl)(1-ethoxycarbonylpiperidin-4-yl)amine: Rf =0.29 (silica gel, ethyl acetate).

1. temperatureCool in an ice bath
2. waitAfter 56 hours
3. additionadd ice
4. customEvaporate the reaction mixture
5. customto remove most of the tetrahydrofuran
6. additiondilute with ethyl acetate
7. extractionextract with a saturated aqueous sodium bicarbonate solution, water
8. dry with materialDry the organic layer over MgSO4
9. filtrationfilter
10. customevaporate in vacuo
11. customto give a residue