Acetic Acid → HCID 66591406, compound

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).

1. extractionthe product was extracted with dichloromethane
2. washThe organic layer was washed with brine solution
3. dry with materialdried over sodium sulfate
4. concentrationconcentrated under reduced pressure
5. customThe resulting transparent viscous liquid was purified by column chromatography
6. concentrationThe reaction mixture was concentrated under reduced pressure
7. washthe resulting residue was washed with ether
8. customdried

ORD record

ord-1402c0eb532f4272b98244bdfb516748

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08129376B2