Sodium hydride → Tert-butyl 4-(3-chloro-4-nitrophenoxy)piperidine-1-carboxylate

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tert-Butyl 4-(4-amino-3-chlorophenoxy)piperidine-1-carboxylate was prepared in the same manner as tert-Butyl 4-(3-(4-amino-5-chloro-2 methylphenoxy)propyl)piperazine-1-carboxylate. Reaction of N-Boc-4-hydroxypiperidine with sodium hydride in anhydrous THF, followed by 2-chloro-4-fluoro-1-nitrobenzene (commercially available from Acros) gave tert-butyl 4-(3-chloro-4-nitrophenoxy)piperidine-1-carboxylate. Reduction of the tent-butyl 4-(3-chloro-4-nitrophenoxy)piperidine-1-carboxylate using ammonium formate and iron dust in refluxing toluene-water mixture gave tert-butyl 4-(4-amino-3-chlorophenoxy)piperidine-1-carboxylate in 79% yield. 1H-NMR (400 MHz, CDCl3): δ 6.88 (m, 1H), 6.70 (m, 2H), 4.26 (m, 1H), 3.79 (s, br, 2H), 3.68 (m, 2H), 3.30 (m, 2H), 1.86 (m, 2H), 1.71 (m, 2H), 1.56 (s, 9H). MS (EI): 227 (MH+).

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