反应详情

Combine 1-(t-butoxycarbonyl)-4-(1-(2-hydroxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepane (1.7 g, 4.7 mmol), tetrahydrofuran (70 mL), and dimethylformamide (8 mL). Cool in an ice bath. Add with stirring, sodium hydride (0.28 g, 60% in oil, 7.0 mmol). After 3 hours, warm to ambient temperature. After 30 minutes, again cool in an ice bath and add bromoacetonitrile (1.12 g, 9.36 mmol). Warm to ambient temperature. After 18 hours, again cool in an ice bath and add a saturated aqueous solution of ammonium chloride (5 mL) and then water (5 mL). Concentrate the reaction mixture in vacuo to remove most to the tetrahydrofuran and dilute with dichloromethane (150 mL). Extract three times with water, dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with ethyl acetate to give 1-(t-butoxycarbonyl)-4-(1-(2-cyanomethyloxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepane: Rf =0.38 (silica gel, ethyl acetate).

1. temperatureCool in an ice bath
2. additionAdd
3. waitAfter 30 minutes
4. temperatureagain cool in an ice bath
5. temperatureWarm to ambient temperature
6. waitAfter 18 hours
7. temperatureagain cool in an ice bath
8. concentrationConcentrate the reaction mixture in vacuo
9. customto remove most to the tetrahydrofuran
10. additiondilute with dichloromethane (150 mL)
11. extractionExtract three times with water
12. dry with materialdry the organic layer over Na2SO4
13. filtrationfilter
14. customevaporate in vacuo
15. customto give a residue