1-(2-Methoxyphenyl)piperazine → [1-(4-Chloro-phenyl)-cyclobutyl]-{3-[4-(2-methoxy-phenyl)-piperazin-1-ylmethyl]piperidin-1-yl}-methanone

HRID 586382Notes

Reaction equation

HRID 586382 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:12]([N:14]3[CH2:19][CH2:18][CH2:17][CH:16]([CH2:20]OS(C)(=O)=O)[CH2:15]3)=[O:13])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[CH3:26][O:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1.C(N(CC)CC)C>C(#N)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:12]([N:14]3[CH2:19][CH2:18][CH2:17][CH:16]([CH2:20][N:37]4[CH2:38][CH2:39][N:34]([C:29]5[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=5[O:27][CH3:26])[CH2:35][CH2:36]4)[CH2:15]3)=[O:13])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 13461-(2-Methoxyphenyl)piperazineHCID 8471TriethylamineHCID 12992442Methanesulfonic acid 1-[1-(4-chloro-phenyl)-cyclobutanecarbonyl]-piperidin-3-ylmethyl ester

Product 1

HCID 9891394[1-(4-Chloro-phenyl)-cyclobutyl]-{3-[4-(2-methoxy-phenyl)-piperazin-1-ylmethyl]piperidin-1-yl}-methanoneYield 43.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2 (1.0 g, 2.60 mmol) in acetonitrile (25 mL) was added 1-(2-methoxyphenyl)piperazine (0.55 g, 2.86 mmol) and triethylamine (2 mL). The reaction was stirred and refluxed for 20 h. After cooling to room temperature, most of solvent was removed by rotary evaporation. The reaction mixture was partitioned between dichloromethane and water (50 mL each), and the organic layer was washed with sat. sodium carbonate (50 mL) and water. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated by rotary evaporation. The organic residue was purified by flash chromatography on silica gel, eluting with dichloromethane/2.0 M ammonia in ethyl alcohol (96:4) to give 3 (0.54 g, 43%) as a light brown solid; C28H36ClN3O2, LRMS (m/z)=483 (MH+).

Workup

  1. temperaturerefluxed for 20 h
  2. customwas removed by rotary evaporation
  3. customThe reaction mixture was partitioned between dichloromethane and water (50 mL each)
  4. washthe organic layer was washed with sat. sodium carbonate (50 mL) and water
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated by rotary evaporation
  8. customThe organic residue was purified by flash chromatography on silica gel
  9. washeluting with dichloromethane/2.0 M ammonia in ethyl alcohol (96:4)

Sources & evidence

ORD record
ord-443be508cd2f48dd8b11eb1c982ad6a7
Source dataset
uspto-grants-2005_08
Patent number
US06936614B2

Reaction notes

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