Nitrogen → 1,1-Dimethylethyl (3R,4S)-4-amino-3-fluoro-1-piperidinecarboxylate

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Reaction Steps

In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), to a solution of tert-butyl 3-fluoro-4-oxopiperidine-1-carboxylate (0.80 g, 3.68 mmol) in MeOH (10 mL) was added ammonium acetate (1.99 g, 25.80 mmol) and the resulting solution stirred at rt for 2 h. NaCNBH3 (0.29 g, 4.42 mmol) was then added and the solution stirred at rt overnight. The reaction mixture was concentrated to dryness and the organics extracted with EA from a 1% aq. solution of Na2CO3. The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified with FC (CH2Cl2/MeOH, 9:1) to afford trans-tert-butyl 4-amino-3-fluoropiperidine-1-carboxylate and cis-tert-butyl 4-amino-3-fluoropiperidine-1-carboxylate both as colorless oils which solidified upon standing. LC-MS-conditions 08: tR=0.48 min; [M-CH3+H]+=204.25 and tR=0.46; [M+H]+=219.26; TLC: rf (CH2Cl2/MeOH, 9:1)=0.30 and 0.09.

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