Acetic Acid → HCID 66591406, compound

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 2,4-dimethylaniline (0.73 g, 0.00602 mole), followed by acetic acid (0.301 g, 0.005 mole) and sodium triacetoxyborohydride (1.596 g, 0.00753 mole) portionwise. The resulting mixture was stirred at ambient temperature for a further 16 hours. The reaction mixture was basified with sodium bicarbonate solution and the product was extracted with dichloromethane. The organic layer was washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure. The resulting transparent viscous liquid was purified by column chromatography using neutral aluminium oxide (1% ethyl acetate in hexane) to 1.5 g (82%) of 4-(2,4-dimethyl-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester. 1H NMR (CDCl3): δ 6.9 (d, 2H), 6.6 (d, 1H), 4.1 (bs, 2H), 3.4 (m, 1H), 3.2 (bs, 1H), 2.9 (t, 2H), 2.2 (s, 3H), 2.1 (s, 3H), 2.1 (s, 3H), 2.0 (s, 2H), 1.5 (s, 9H), 1.4-1.2 (m, 2H). A solution of 4-(2,4-dimethyl-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester (1.26 g, 0.00413 mole) in ethyl acetate.HCl (10 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 1.12 g (97%) of (2,4-dimethyl-phenyl)-piperidin-4-yl-amine dihydrochloride. LCMS: 205.16 (M+1)+, 95.9%. 1H NMR (DMSO-d6): δ 9.2 (d, 1H), 8.2 (d, 1H), 7.2 (m, 3H), 3.7 (m, 3H), 3.3 (d, 3H), 3.0 (q, 2H), 2.3 (m, 5H), 2.1 (d, 2H), 1.9 (d, 2H).

Provenance & Evidence