Water → N-Ethyl-1,2,3,6-tetrahydro-4-(3-(1-methylethoxy)phenyl)pyridine

HRID 397737Notes

Reaction equation

HRID 397737 reaction equation
C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH2:12]([N:14]1[CH2:19][CH2:18][C:17](O)([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26][CH:27]([CH3:29])[CH3:28])[CH:21]=2)[CH2:16][CH2:15]1)[CH3:13].O.[OH-].[Na+]>C1(C)C=CC=CC=1>[NH3:14].[CH2:12]([N:14]1[CH2:15][CH:16]=[C:17]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26][CH:27]([CH3:28])[CH3:29])[CH:21]=2)[CH2:18][CH2:19]1)[CH3:13]

Participants

7

Reactant 4

HCID 962WaterHCID 6101p-Toluenesulfonic acidHCID 14798Sodium HydroxideHCID 22707912N-Ethyl-4-hydroxy-4-(3-(1-methylethoxy)phenyl)piperidine

Product 2

HCID 222AmmoniaHCID 22707935N-Ethyl-1,2,3,6-tetrahydro-4-(3-(1-methylethoxy)phenyl)pyridineYield 107%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

p-Toluenesulfonic acid (6.1 g, 31.9 mmoi) was added to a solution of N-ethyl-4-hydroxy-4-(3-(1-methylethoxy)phenyl)piperidine (Preparation 43, 4.2 g, 16.0 mmol) in toluene (50 ml), and the reaction mixture was heated under reflux for 3 h. The reaction mixture was allowed to cool to room temperature, water (20 ml) was added, and the resultant biphasic system was stirred vigorously for several minutes. The aqueous layer was basified with 2N aqueous sodium hydroxide solution (10 ml) and the two phases were separated. The aqueous layer was then further extracted with ether (3×10 ml) and the combined extracts were dried (MgSO4), filtered and concentrated to give a crude oil which was purified by silica column chromatography eluting with ethyl acetate:methanol: 0.880 ammonia (96:3:1) to give the title compound as an oil (2.1 g, 54%).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureunder reflux for 3 h
  3. customthe two phases were separated
  4. extractionThe aqueous layer was then further extracted with ether (3×10 ml)
  5. dry with materialthe combined extracts were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a crude oil which
  9. customwas purified by silica column chromatography
  10. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-86fb28e004be4ee79e2b8ea8e0938f83
Source dataset
uspto-grants-2003_08
Patent number
US06610711B2

Reaction notes

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