反应详情

To a solution of 1-(2-Methoxy-ethyl)-piperidin-4-ol (5.74 mmol) in THF (20 mL) was added NaH (11.6 mmol). Note: excess NaH was added due to excess tButyl ethyl malonate carried over from 2a. The solution was agitated for 10 minutes. A solution of 2a/2b/malonate (5.15 mmol, corrected for assay) in THF (20 mL) was rapidly added to the first solution. The resulting solution was agitated at 30° C. for 18 hours, then at 55° C. for 2 hours. After allowing to cool to room temperature, the solution was quenched with water (400 μL), dried over Na2SO4 and concentrated in vacuo yielding a yellow oil which was purified by flash chromatography (silica, Gradient system: 1. Ethyl acetate, 2. 10% Methanol in Ethyl acetate). Upon concentration a yellow oil 3 (1.096 g, 45.2% yield) with an isomeric ratio of 3.3:1 was obtained.

1. stirringThe resulting solution was agitated at 30° C. for 18 hours
2. waitat 55° C. for 2 hours
3. customthe solution was quenched with water (400 μL)
4. dry with materialdried over Na2SO4
5. concentrationconcentrated in vacuo
6. customyielding a yellow oil which
7. customwas purified by flash chromatography (silica, Gradient system: 1. Ethyl acetate, 2. 10% Methanol in Ethyl acetate)