1-(2-Methoxyphenyl)piperazine → 1-{1-[1-(4-Choro-phenyl)-cyclopropylmethyl]-piperidin-3ylmethyl}-4-(2-methoxy-phenyl)-piperazine

HRID 1788083Notes

Reaction equation

HRID 1788083 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:11][N:12]3[CH2:17][CH2:16][CH2:15][CH:14]([CH2:18]OS(C)(=O)=O)[CH2:13]3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[CH3:24][O:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([CH2:11][N:12]3[CH2:17][CH2:16][CH2:15][CH:14]([CH2:18][N:35]4[CH2:34][CH2:33][N:32]([C:27]5[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=5[O:25][CH3:24])[CH2:37][CH2:36]4)[CH2:13]3)[CH2:9][CH2:10]2)=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 13461-(2-Methoxyphenyl)piperazineHCID 11430Potassium CarbonateHCID 21303197Methanesulfonic acid 1-[1-(4-chloro-phenyl)-cyclopropylmethyl]-piperidin-3-ylmethyl ester

Product 1

HCID 129924521-{1-[1-(4-Choro-phenyl)-cyclopropylmethyl]-piperidin-3ylmethyl}-4-(2-methoxy-phenyl)-piperazineYield 54.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of methanesulfonic acid 1-[1-(4-chloro-phenyl)-cyclopropylmethyl]-piperidin-3-ylmethyl ester (2.94 g, 8.20 mmol) in acetonitrile (40.0 mL) at room temperature was added 1-(2-methoxy-phenyl)-piperazine (1.58 g, 8.20 mmol) followed by potassium carbonate (13.35 g, 41.0 mmol). The reaction mixture was refluxed overnight. After cooling down to room temperature the reaction mixture was diluted with water and extracted with EtOAc (3×50 mL). The combined organic layers were dried over sodium sulfate and concentrated to yield a crude oil. The resulting residue was purified by silica gel chromatography (96:4 DCM: 2M NH3 in EtOH) to obtain the desired compound as an oil (2.04 g). 13C NMR (100 MHz, CDCl3) δ 152.5, 143.9, 141.8, 131.5, 130.4, 128.2, 123.1, 121.3, 118.4, 111.5, 67.8, 63.0, 59.5, 55.6, 55.2, 54.2, 51.0, 33.5, 29.8, 25.2, 23.1, 13.4, 13.1.

Workup

  1. temperatureThe reaction mixture was refluxed overnight
  2. extractionextracted with EtOAc (3×50 mL)
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. concentrationconcentrated
  5. customto yield a crude oil
  6. customThe resulting residue was purified by silica gel chromatography (96:4 DCM: 2M NH3 in EtOH)

Sources & evidence

ORD record
ord-eeb8b540ab9d40e081dbf145739db960
Source dataset
uspto-grants-2009_03
Patent number
US07511141B2

Reaction notes

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