反应详情

1-Hydroxybenzotriazole (0.183 g, 0.0012 mol) is added to a stirred solution of 1-{4-[5-(2-fluoro-biphenyl-4-yl)-[1,2,4]oxadiazol-3-yl]-benzyl}-piperidine-4,4-dicarboxylic acid benzyl ester (0.6 g, 0.0010 mol) in tetrahydrofuran (20 mL). Reaction mixture is stirred for 30 minutes at room temperature. Morpholine (0.13 mL, 0.0015 mol) and 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (0.288 g, 0.0015 mol) are added to the reaction mixture and stirred for over night at room temperature. Demineralized water (10 mL) is added to the reaction mixture, tetrahydrofuran layer is separated and the aqueous layer is extracted with ethyl acetate (2×15 mL). Combined organic layer is dried over sodium sulphate and concentrated under reduced pressure to yield a crude viscous liquid, which is purified by column chromatography (silica gel 230-400 mesh, ethyl acetate) to get 1-{4-[5-(2-fluoro-biphenyl-4-yl)-[1,2,4]oxadiazol-3-yl]-benzyl}-4-(morpholine-4-carbonyl)-piperidine-4-carboxylic acid benzyl ester.

1. customReaction mixture
2. stirringstirred for over night at room temperature
3. customis separated
4. extractionthe aqueous layer is extracted with ethyl acetate (2×15 mL)
5. dry with materialCombined organic layer is dried over sodium sulphate
6. concentrationconcentrated under reduced pressure
7. customto yield a crude viscous liquid, which
8. customis purified by column chromatography (silica gel 230-400 mesh, ethyl acetate)