Hydrochloric Acid → (2,5-Dimethyl-phenyl)-piperidin-4-yl-amine dihydrochloride

HRID 1093542Notes

Reaction equation

HRID 1093542 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:20]=[C:19]([CH3:21])[CH:18]=[CH:17][C:16]=2[CH3:22])[CH2:10][CH2:9]1)=O)(C)(C)C.[ClH:23]>C(OCC)(=O)C>[ClH:23].[ClH:23].[CH3:22][C:16]1[CH:17]=[CH:18][C:19]([CH3:21])=[CH:20][C:15]=1[NH:14][CH:11]1[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 665915964-(2,5-Dimethyl-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 66591423(2,5-Dimethyl-phenyl)-piperidin-4-yl-amine dihydrochlorideYield 80%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (1 g, 0.00502 mole) in dry 1,2-dichloroethane (10 mL) was stirred under an atmosphere of nitrogen for 10 minutes. 2,5-dimethylaniline (0.73 g, 0.00602 mole), acetic acid (0.301 g, 0.005 mole) and sodium triacetoxyborohydride (1.596 g, 0.00753 mole) were then added portionwise and stirring was continued at ambient temperature for 16 hours. The reaction mixture was basified with sodium bicarbonate solution and the product was extracted with dichloromethane. The dichloromethane 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 afford 1.5 g (82%) of 4-(2,5-dimethyl-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester. 1H NMR (CDCl3): δ 7.0 (t, 1H), 6.6 (d, 2H), 4.2 (dd, 2H), 3.5 (m, 1H), 2.9 (t, 2H), 2.3 (t, 3H), 2.15 (s, 3H), 2.05 (s, 3H), 1.5 (s, 9H), 1.3 (t, 2H). A solution of 4-(2,5-dimethyl-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester (1.5 g, 0.00492 mole) in ethyl acetate.HCl (7 mL) was stirred at ambient temperature for 2 hours. The reaction mixture was concentrated under reduced pressure and the residue was washed with ether and dried to afford 1.1 g (80%) of (2,5-dimethyl-phenyl)-piperidin-4-yl-amine dihydrochloride. LCMS: 205.16 (M+1)+, 92.74%, 1H NMR (DMSO-d6): δ 9.4 (d, 1H), 9.0 (d, 1H), 7.2 (d, 2H), 7.1 (s, 1H), 3.7 (m, 1H), 3.6 (s, 1H), 3.4 (d, 2H), 3.2 (bs, 1H), 2.9 (m, 2H), 2.4 (s, 3H), 2.3 (s, 3H), 2.1 (m, 4H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. washthe residue was washed with ether
  3. customdried

Sources & evidence

ORD record
ord-105b6f588eb04cf0bfe5dc308cf4f43f
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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