Acetic Acid → tert-Butyl 4-((2-bromophenyl)amino)piperidine-1-carboxylate

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Reaction Steps

To a stirred solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (0.5 g, 0.0025 mole) in dry 1,2-dichloroethane (5 mL) under an atmosphere of nitrogen was added 2-bromoaniline (0.474 g, 0.00276 mole), acetic acid (0.18 g, 0.00301 mole) and sodium triacetoxyborohydride (0.638 g, 0.00301 mole). Stirring was continued at ambient temperature for 14 hours. The reaction mixture was quenched in cold aqueous 1N NaOH solution and the product extracted with ether. The organic layer was washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure to afford the crude product as transparent viscous liquid. Purification by column chromatography using silica gel 60-120 mesh (2% ethyl acetate in hexane) afforded 0.320 g (35%) of desired 4-(2-bromo-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester. 1H NMR (DMSO-d6): δ 7.44-7.38 (m, 1H), 7.2-7.12 (m, 1H), 6.84-6.78 (m, 1H), 6.58-6.48 (m, 1H), 4.65 (d, 1H), 3.9 (m, 2H), 3.5 (m, 1H), 3.0-2.8 (m, 2H), 2.0-1.8 (m, 2H), 1.4 (s, 9H). To a cooled solution (0° C.) of 4-(2-bromo-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester (0.31 g, 0.00087 mole) in dioxane (0.5 mL) was added dioxane.HCl (2.5 mL). The mixture was stirred at the same temperature for 10 minutes, then gradually brought to ambient temperature with continued stirring for a further 15 minutes. The reaction mixture was evaporated under reduced pressure to afford a residue which was washed with dry ether to afford 0.106 g (42%) of 2-bromo-phenyl)-piperidin-4-yl-amine dihydrochloride.

Provenance & Evidence