Piperidine → 3-Amino-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid

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Reaction Steps

1-(tert-butoxycarbonyl)-3-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}piperidine-3-carboxylic acid was resolved by chiral HPLC resolution {Merck 50 mm 16 μm Kromasil Chirose 2 No. CT9014, tert-butylmethylether/iso-propanol (90/10). The first eluted enantiomer (800 mg, 1.71 mmol) 1-(tert-butoxycarbonyl)-3-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}piperidine-3-carboxylic acid (Isomer 1) was dissolved in N,N-dimethylformamide (10 ml) and piperidine (0.85 ml, 8.55 mmol) added. The mixture was stirred at room temperature over night. The resulting white precipitate was filtered off. The filtrates were concentrated and the residues purified by column chromatography on silica eluting with saturated ammonia in methanol/dichloromethane (25/75). The fractions containing the desired product were combined with the filtered solids and evaporated to give 3-amino-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid (Isomer 1) (339 mg, 81%); 1H NMR Spectrum: (D2O) 1.44 (s, 9H); 1.63 (m, 1H); 1.79 (d, 1H); 1.97 (d, 1H); 2.10 (m, 1H); 2.88 (t, 1H); 3.33 (d, 1H); 4.09 (m, 2H).

Provenance & Evidence