Cl.[CH3:2][O:3][C:4]([CH:6]1[C:11](=[O:12])[CH2:10][CH2:9][N:8]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:7]1)=[O:5].[H-].[Na+].[CH2:22](Br)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.O>CN(C=O)C.C(OCC)(=O)C>[CH3:2][O:3][C:4]([C:6]1([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:11](=[O:12])[CH2:10][CH2:9][N:8]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:7]1)=[O:5]1-Benzyl-4-oxo-piperidine-3-carboxylic acid methyl ester hydrochloride salt (1, Z=benzyl) (15 g, 52.9 mmol) was suspended in DMF (150 mL) and cooled to 0° C. Sodium hydride (4.23 g, 105.8 mmol) was added portionwise over 1 h and the contents were allowed to warm to ambient temperature and stir for a further 1 h. Benzyl bromide (6.3 mL, 53.0 mmol) was added over 15 min and the contents were stirred for a further 68 h at ambient temperature. 10 mL of water were added and the contents were diluted with 400 mL of ethyl acetate, washed with water (200 mL), saturated sodium bicarbonate (200 mL) and brine (200 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated to give 20.5 g yellow oil that was purified by flash column chromatography (3:2 cyclohexane/CH2Cl2 to 100% CH2Cl2) to give 17.52 g (98%) of the title compound as a colorless oil. LC-MS: RT=2.80 min. (M+H)+ 338, (M-OMe)+ 306.
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