Cl.[NH2:2][C@@H:3]1[C@@H:8]2[CH2:9][C@@H:5]([CH2:6][CH2:7]2)[C@@H:4]1[C:10]([O:12][CH3:13])=[O:11].C([O-])(=O)C.[Na+].[F:19][C:20]1[CH:27]=[CH:26][C:23]([CH:24]=O)=[CH:22][CH:21]=1.C([BH3-])#N.[Na+].C(=O)(O)[O-].[Na+]>CO.C(OCC)(=O)C>[F:19][C:20]1[CH:27]=[CH:26][C:23]([CH2:24][NH:2][C@@H:3]2[C@@H:8]3[CH2:9][C@@H:5]([CH2:6][CH2:7]3)[C@@H:4]2[C:10]([O:12][CH3:13])=[O:11])=[CH:22][CH:21]=1Methyl (1R,2S,3R,4S)-3-aminobicyclo[2.2.1]heptane-2-carboxylate hydrochloride (0.5 g, 2.43 mmol) was dissolved in methanol (12 mL). Sodium acetate (0.4 g, 4.86 mmol) was added followed by 4 Å powdered molecular sieves (0.5 g) and 4-fluoro-benzaldehyde (0.302 g, 2.43 mmol). Sodium cyanoborohydride (0.305 g, 4.86 mmol) was added and the mixture was stirred at 25° C. for 3 h. The mixture was poured into ethyl acetate (300 mL) and shaken with saturated aqueous sodium bicarbonate solution (200 mL). Both layers were passed through a plug of Celite. The organic layer was further washed with saturated aqueous sodium bicarbonate solution (100 mL), saturated aqueous brine solution (100 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo to afford the crude product, methyl (1R,2S,3R,4S)-3-[(4-fluorobenzyl)amino]bicyclo[2.2.1]heptane-2-carboxylate (0.675 g, 2.43 mmol, 99%), as a clear oil. LC-MS (ESI) calcd for C16H20FNO2 277.15, found 278.2 [M+H+].
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