Water → 1-[2-[3-(3,4-Dichloro-phenyl)-1-(2,4-dimethoxy-benzoyl)-pyrrolidin-3-yl]-ethyl]-4-phenyl-piperidine-4-carboxylic acid amide

HRID 265915

Reaction equation

HRID 265915 reaction equation
[CH3:1][O:2][C:3]1[CH:30]=[C:29]([O:31][CH3:32])[CH:28]=[CH:27][C:4]=1[C:5]([N:7]1[CH2:11][CH2:10][C:9]([CH2:20][CH2:21]CS([O-])(=O)=O)([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([Cl:19])[CH:13]=2)[CH2:8]1)=[O:6].Cl.[C:34]1([C:40]2([C:46]([NH2:48])=[O:47])[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]2)[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C(=O)([O-])[O-].[K+].[K+].O>C1COCC1>[Cl:19][C:14]1[CH:13]=[C:12]([C:9]2([CH2:20][CH2:21][N:43]3[CH2:42][CH2:41][C:40]([C:34]4[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=4)([C:46]([NH2:48])=[O:47])[CH2:45][CH2:44]3)[CH2:10][CH2:11][N:7]([C:5](=[O:6])[C:4]3[CH:27]=[CH:28][C:29]([O:31][CH3:32])=[CH:30][C:3]=3[O:2][CH3:1])[CH2:8]2)[CH:17]=[CH:16][C:15]=1[Cl:18]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 30171294-Phenylpiperidine-4-carboxamide monohydrochlorideHCID 867509052-[1-(2,4-Dimethoxy-benzoyl)-3-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethyl-methanesulfonate

Product 1

HCID 442122841-[2-[3-(3,4-Dichloro-phenyl)-1-(2,4-dimethoxy-benzoyl)-pyrrolidin-3-yl]-ethyl]-4-phenyl-piperidine-4-carboxylic acid amideYield 36.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-[1-(2,4-Dimethoxy-benzoyl)-3-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethyl-methanesulfonate (343 mg, 0.68 mmol) was dissolved in THF (8 mL) and the 4-phenyl-piperidine-4-carboxylic acid amide hydrochloride (170 mg, 0.71 mmol, 1.04 eq.), potassium carbonate (200 mg, 1.45 mmol, 2.1 eq.), and water (2 mL) were added and the solution was heated at reflux for 16 hours. The solution was concentrated in vacuo and the aqueous phase was extracted with dichloromethane, dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was chromatographed on silica gel (40 g) with a gradient of ethyl acetate to 6% methanol in dichloromethane to give 151 mg (36%) of the title compound.

Workup

  1. temperaturethe solution was heated
  2. temperatureat reflux for 16 hours
  3. concentrationThe solution was concentrated in vacuo
  4. extractionthe aqueous phase was extracted with dichloromethane
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was chromatographed on silica gel (40 g) with a gradient of ethyl acetate to 6% methanol in dichloromethane

Sources & evidence

ORD record
ord-7bb48001271a4aa088cae18790e56ed0
Source dataset
uspto-grants-1997_07
Patent number
US05648366

Linked notes

Loading…