[CH3:1][O:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][CH:8]([OH:11])[CH2:7][CH2:6]1.[H-].[Na+].C(OCC)(=O)CC([O-])=O.[CH2:23]([O:25][C:26](=[O:45])[CH:27]([C:35]1[C:40]([N+:41]([O-:43])=[O:42])=[CH:39][CH:38]=[C:37](Cl)[N:36]=1)[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH3:24].C([O-])(=O)CC([O-])=O>C1COCC1>[CH2:23]([O:25][C:26](=[O:45])[CH:27]([C:35]1[C:40]([N+:41]([O-:43])=[O:42])=[CH:39][CH:38]=[C:37]([O:11][CH:8]2[CH2:7][CH2:6][N:5]([CH2:4][CH2:3][O:2][CH3:1])[CH2:10][CH2:9]2)[N:36]=1)[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH3:24]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.
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