O=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])(C)C)=[O:9])[CH2:4][CH2:3]1.[CH:15]1[CH:20]=[CH:19]N=[CH:17][CH:16]=1.[FH:21].C(OC(ON1C(=O)CC[C:34]1=[O:39])=O)C1C=CC=CC=1>C(Cl)Cl>[F:21][C:2]1([CH2:34][OH:39])[CH2:3][CH2:4][N:5]([C:8]([O:10][CH2:11][C:14]2[CH:19]=[CH:20][CH:15]=[CH:16][CH:17]=2)=[O:9])[CH2:6][CH2:7]1To a solution of tert-butyl 4-oxopiperidine-1-carboxylate (7.0 g, 32.8 mmol) in CH2Cl2 (14 mL) at −10° C. was added HF-pyridine (11.6 mL, 82.1 mmol) portionwise. The reaction mixture was stirred for 10 min at −10° C., warmed to RT. After stirring for 16 h, the reaction was quenched with aqueous NaCO3, and extracted with CH2Cl2. The aquoues layer was concentrated to a white paste that was suspended in CH2Cl2 (100 mL). N-benzyloxycarbonyloxysuccinimide (8.2 g, 32.8 mmol) was added and the mixture was stirred at RT for 3 h. The reaction mixture was partitioned between EtOAc and H2O, the organic layer was dried over Na2SO4, filtered and concentrated. Purification on silica gel (10:1 to 1:1 hexanes:EtOAc) gave benzyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate as a clear oil. M.S. (M+1): 268
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