tert-Butyl 4-oxopiperidine-1-carboxylate → HCID 59865005、化合物
反応式
I[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][CH2:10][CH2:11][N:12]2[CH2:17][CH2:16][CH2:15][C:14]([CH3:19])([CH3:18])[CH2:13]2)=[CH:4][CH:3]=1.[Li]CCCC.[C:25]([N:32]1[CH2:37][CH2:36][C:35](=[O:38])[CH2:34][CH2:33]1)([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26]>C1COCC1>[CH3:18][C:14]1([CH3:19])[CH2:15][CH2:16][CH2:17][N:12]([CH2:11][CH2:10][CH2:9][O:8][C:5]2[CH:6]=[CH:7][C:2]([C:35]3([OH:38])[CH2:34][CH2:33][N:32]([C:25]([O:27][C:28]([CH3:30])([CH3:29])[CH3:31])=[O:26])[CH2:37][CH2:36]3)=[CH:3][CH:4]=2)[CH2:13]1参加物
5
実験手順
A solution of 1-{3-[(4-iodophenyl)oxy]propyl}-3,3-dimethylpiperidine (for example as prepared for Intermediate 2) (3 g, 8.02 mmol) in anhydrous THF (30 ml) was cooled to −78° C. under nitrogen and treated with nBuLi (1.6M solution in hexanes, 6.02 ml, 9.63 mmol), after 0.5 h, a solution of N-Boc-4-oxopiperidine (commercially available, for example from Aldrich) (1.99 g, 10 mmol) in THF (10 ml) was added dropwise. The mixture was allowed to warm up to room temperature and was stirred overnight. The mixture was quenched with ammonium chloride solution and extracted with EtOAc, dried over magnesium sulphate, filtered and concentrated. The resulting residue was purified by FlashMaster II chromatography using a 100 g cartridge, eluting with 100% cyclohexane for 5 minutes, 100% cyclohexane to 100% EtOAc over 15 minutes, 100% EtOAc to 100% DCM in 5 minutes and 100% DCM to 30% MeOH (containing 1% of triethylamine) in DCM over 40 minutes then held constant for 5 min, monitoring at 254 nm to afford the title compound (1.25 g). LCMS RT=2.48 min, ES+ve m/z 447 (M+H)+.