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) (0.05 g, 0.09 mmol) and tetrahydrofuran (5 mL). Cool to −78° C. using a dry-ice/acetone bath. Add dropwise a solution of sec-butyllithium (0.15 mL, 1.3 M, 0.19 mmol). When the addition of sec-butyllithium is complete, add a solution 2-methylsulfonylethyl mesylate (0.02 g, 0.10 mmol) in tetrahydrofuran (2 mL). Heat the reaction mixture to reflux. After 12 hours, cool, add sec-butyllithium (0.10 mL) and 2-methylsulfonylethyl mesylate (0.02 g, 0.10 mmol) and again heat the reaction mixture to reflux. After 12 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 0.5% concentrated aqueous ammonia solution/5% methanol/dichloromethane to give the title compound: Rf=0.38 (silica gel, 0.5% concentrated aqueous ammonia solution/5% methanol/dichloromethane).

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