Acetic Acid → 4-(2,3-Dimethyl-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Steps

To a stirred solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (1 g, 0.00502 mole) in dry 1,2-dichloroethane (10 mL) (under an atmosphere of nitrogen for 10 minutes) was added 2,3-dimethylaniline (0.73 g, 0.00602 mole), acetic acid (0.301 g, 0.005 mole) and sodium triacetoxyborohydride (1.596 g, 0.00753 mole) portionwise with stirring. The stirring was continued at ambient temperature for a further 16 hours. The reaction mixture was basified with sodium bicarbonate solution and the product extracted with dichloromethane. The dichloromethane layer was washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure to as afford a transparent viscous liquid which was purified by column chromatography using neutral aluminium oxide (1% ethyl acetate in hexane) to afford 1.5 g (98%) of 4-(2,3-dimethyl-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester. 1H NMR (CDCl3): δ 7.0 (t, 1H), 6.6 (m, 2H), 4.1 (m, 2H), 3.5 (m, 1H), 3.0-2.9 (t, 2H), 2.3 (s, 3H), 2.1 (m, 2H), 2.0 (s, 3H), 1.5 (s, 9H), 1.4 (m, 2H). A solution of 4-(2,3-dimethyl-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester (1.45 g, 0.00476 mole) in ethyl acetate.HCl (15 mL) was stirred at ambient temperature for 2 hours. The reaction mixture was concentrated under reduced pressure and the resulting residue was washed with ether and dried to afford 1.1 g (83) of (2,3-dimethyl-phenyl)-piperidin-4-yl-amine dihydrochloride. LCMS: 205.16 (M+1)+, 95.98%, 1H NMR (DMSO-d6): δ 9.4 (d, 1H), 9.0 (d, 1H), 7.3 (m, 3H), 3.7 (m, 2H), 3.3 (d, 2H), 3.1 (bs, 1H), 2.9 (m, 2H), 2.3 (d, 6H), 2.1 (m, 4H).

Provenance & Evidence