1-Phenethylamine, (+)- → (R)-5-(1-phenyl-ethylamino)-3,6-dihydro-2H-pyridine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester

HRID 1169211Notes

Reaction equation

HRID 1169211 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:10](=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:20][C@@H:21]([NH2:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C1(C)C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH2:17]([O:16][C:14]([C:11]1[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][C:10]=1[NH:28][C@@H:21]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH3:20])=[O:15])[CH3:18]

Participants

5

Reactant 2

HCID 6431891-Phenethylamine, (+)-HCID 158529891-tert-Butyl 4-ethyl 3-oxopiperidine-1,4-dicarboxylate

Product 1

HCID 16099094(R)-5-(1-phenyl-ethylamino)-3,6-dihydro-2H-pyridine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl esterYield 100.2%

Reagents, catalysts & solvents 2

HCID 521998p-Toluenesulfonic acid monohydrateCatalystHCID 1140TolueneSolvent

Procedure

In a dry flask equipped with a Dean-Stark trap and reflux condenser, ethyl 1-(t-butoxycarbonyl)-3-oxo-4-piperidinecarboxylate (4.19 g, 15.4 mmol) was dissolved in toluene (50 mL). (R)-(+)-a-Methylbenzylamine (1.91 g, 15.8 mmol) and p-toluenesulfonic acid monohydrate (0.019 g, 0.1 mmol) were added and the mixture heated to reflux for 6 hours. The crude reaction mixture was concentrated in vacuo to give the desired amine (5.78 g, 100%) as a thick orange oil. 1H NMR (300 MHz, CDCl3), δ: 7.36 (t, J=3, 2H), 7.33 (t, J=4, 1H), 7.31 (dd, J=3, J′=4, 2H), 4.59 (m, 1H), 4.16 (q, J=7, 2H), 3.59 (m, 2H), 2.34 (m, 2H), 1.58 (bs, 2H), 1.52 (d, J=3, 3H), 1.29 (s, 9H), 1.26 (t, 3H, J=7). MS (ESI), m+/z: (M+H)+=375.

Workup

  1. customIn a dry flask equipped with a Dean-Stark trap
  2. temperaturereflux condenser
  3. temperaturethe mixture heated
  4. temperatureto reflux for 6 hours
  5. customThe crude reaction mixture
  6. concentrationwas concentrated in vacuo

Sources & evidence

ORD record
ord-07125872490c46a18442af9e89d7fe85
Source dataset
uspto-grants-2003_09
Patent number
US06627629B2

Reaction notes

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