(4-Chlorobutyl)benzene → 2-methyl-N-{3-[1-(4-phenylbutyl)-4-piperidinyl]phenyl}propanamide

HRID 2087161Notes

Reaction equation

HRID 2087161 reaction equation
[CH3:1][CH:2]([CH3:18])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[CH:7]=1)=[O:4].[C:19]1([CH2:25][CH2:26][CH2:27][CH2:28]Cl)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(N(C(C)C)CC)(C)C>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCOCC1>[CH3:1][CH:2]([CH3:18])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH:12]2[CH2:17][CH2:16][N:15]([CH2:28][CH2:27][CH2:26][CH2:25][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:14][CH2:13]2)[CH:7]=1)=[O:4]

Participants

6

Reactant 3

HCID 78543(4-Chlorobutyl)benzeneHCID 81531DiisopropylethylamineHCID 167572552-methyl-N-[3-(4-piperidyl)phenyl]propanamide

Product 1

HCID 220491282-methyl-N-{3-[1-(4-phenylbutyl)-4-piperidinyl]phenyl}propanamideYield 25.1%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide (28.3 mg, 0.100 mmol), 4-phenyl-1-chlorobutane (21.1 mg, 0.125 mmol), diisopropylethylamine (0.50 mL), catalytic amount of tetrabutylammonium iodide and dioxane (2.0 mL) was heated at reflux temperature for 3 days. The reaction mixture was concentrated and chromatographed using preparative TLC plates [2.5% of NH3 (2.0 M in methanol) in CHCl3] afforded the product, 2-methyl-N-{3-[1-(4-phenylbutyl)-4-piperidinyl]phenyl}propanamide (9.50 mg, 25.1% yield) as a thick oil: 1H NMR δ 7.37 (s, 1H), 7.29 (apparent d, 1H, J=7.9 Hz), 7.18 (m, 3H), 7.11 (m, 3H), 6.90 (apparent d, 1H, J=7.9 Hz), 3.02 (d, 2H, J=6.8 Hz), 2.41 (m, 4H, partially hidden), 2.01 (m, 2H), 1.78 (m, 4H), 1.57 (m, 4H), 1.18 (d, 6H, J=7.7 Hz); ESMS m/e: 379.4 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux temperature for 3 days
  3. concentrationThe reaction mixture was concentrated
  4. customchromatographed

Sources & evidence

ORD record
ord-fce91eca80fb4efea2e44b04b7798817
Source dataset
uspto-grants-2004_04
Patent number
US06727264B1

Reaction notes

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