p-Toluenesulfonic acid → 4-{2-[1-(4-Chlorophenyl)ethylamino]ethyl}-1-(2-phenoxyethyl)piperidine

HRID 962451Notes

Reaction equation

HRID 962451 reaction equation
[NH2:1][CH2:2][CH2:3][CH:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([C:17](=O)[CH3:18])=[CH:13][CH:12]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[C:31]1([O:37][CH2:38][CH2:39]Br)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>C(N(CC)CC)C.O.C1(C)C=CC=CC=1>[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([CH:17]([NH:1][CH2:2][CH2:3][CH:4]2[CH2:9][CH2:8][N:7]([CH2:39][CH2:38][O:37][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH2:6][CH2:5]2)[CH3:18])=[CH:13][CH:12]=1

Participants

8

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 7467P-ChloroacetophenoneHCID 68526Benzene, (2-bromoethoxy)-HCID 15126024-Piperidineethanamine

Product 1

HCID 190854494-{2-[1-(4-Chlorophenyl)ethylamino]ethyl}-1-(2-phenoxyethyl)piperidine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8471TriethylamineSolvent

Procedure

In a similar manner to Example 31, a mixture of 4-(2-aminoethyl)piperidine (5.0 g), 4'-chloroacetophenone (6.04 g), p-toluenesulphonic acid (catalytic amount) and toluene (100 ml) was boiled under reflux for 10 hours with water removal using a Dean and Stark apparatus. The mixture was cooled to ambient temperature and 2-bromoethyl phenyl ether (7.85 g) and triethylamine (5.4 ml) added. The mixture was boiled under reflux for 6 hours. The solvent was evaporated off and the residue dissolved in ethanol (100 ml) and sodium borohydride (3.4 g) was added. The mixture was boiled under reflux for 4 hours then worked up to give an oil which was purified by flash column chromatography on silica using ethyl acetate/triethylamine (95:5) as the mobile phase to give 4-{2-[1-(4-chlorophenyl)ethylamino]ethyl}-1-(2-phenoxyethyl)piperidine as an oil.

Workup

  1. temperatureunder reflux for 6 hours
  2. customThe solvent was evaporated off
  3. dissolutionthe residue dissolved in ethanol (100 ml)
  4. additionsodium borohydride (3.4 g) was added
  5. temperatureunder reflux for 4 hours
  6. customto give an oil which
  7. customwas purified by flash column chromatography on silica

Sources & evidence

ORD record
ord-609c2e54f3494a56a3b1d0ca5069470d
Source dataset
uspto-grants-1998_06
Patent number
US05760035

Reaction notes

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