反应详情

温度

-78 °C

Combine 1-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine (prepared from (−)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine(R,R)-di-p-anisoyltartaric acid salt) (0.6 g, 1.0 mmol) and tetrahydrofuran (10 mL). Cool to −78° C. using a dry-ice/acetone bath. Add dropwise a solution of sec-butyllithium (1.26 mL, 1.3 M, 1.64 mmol). When the addition of sec-butyllithium is complete, add a solution ethyl vinyl sulfone (0.37 g, 3.08 mmol) in tetrahydrofuran (2 mL). Heat the reaction mixture to reflux and seal with a rubber septum. After 18 hours, cool, add ethyl vinyl sulfone (0.37 g, 3.08 mmol) and again heat the reaction mixture to reflux. After 6 hours, cool, add water, separate the layers and extract the aqueous layer twice with ethyl acetate. Combine the organic layers, dry over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 0.2% concentrated aqueous ammonia solution/5% methanol/dichloromethane to give the title compound.

1. temperatureHeat the reaction mixture
2. temperatureto reflux
3. customseal with a rubber septum
4. temperaturecool
5. temperatureagain heat the reaction mixture
6. temperatureto reflux
7. waitAfter 6 hours
8. temperaturecool
9. customseparate the layers
10. extractionextract the aqueous layer twice with ethyl acetate
11. dry with materialdry over Na2SO4
12. filtrationfilter
13. customevaporate in vacuo
14. customto give a residue