Potassium Iodide → 1-{2-[2-(3,4-Dichlorophenyl)-4-(3,4,5-trimethoxybenzoyl)morpholin-2-yl]ethyl}-4-phenylpiperidine-4-carboxamide

HRID 1275163Notes

Reaction equation

HRID 1275163 reaction equation
CS(O[CH2:6][CH2:7][C:8]1([C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[C:30]([Cl:35])[CH:29]=2)[O:13][CH2:12][CH2:11][N:10]([C:14](=[O:27])[C:15]2[CH:20]=[C:19]([O:21][CH3:22])[C:18]([O:23][CH3:24])=[C:17]([O:25][CH3:26])[CH:16]=2)[CH2:9]1)(=O)=O.Cl.[C:37]1([C:43]2([C:49]([NH2:51])=[O:50])[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]2)[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.C(=O)([O-])O.[Na+].[I-].[K+]>CN(C)C=O.O>[Cl:35][C:30]1[CH:29]=[C:28]([C:8]2([CH2:7][CH2:6][N:46]3[CH2:45][CH2:44][C:43]([C:37]4[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=4)([C:49]([NH2:51])=[O:50])[CH2:48][CH2:47]3)[O:13][CH2:12][CH2:11][N:10]([C:14](=[O:27])[C:15]3[CH:20]=[C:19]([O:21][CH3:22])[C:18]([O:23][CH3:24])=[C:17]([O:25][CH3:26])[CH:16]=3)[CH2:9]2)[CH:33]=[CH:32][C:31]=1[Cl:34]

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 516892Sodium BicarbonateHCID 30171294-Phenylpiperidine-4-carboxamide monohydrochlorideHCID 577562112-[2-(3,4-Dichlorophenyl)-4-(3,4,5-trimethoxybenzoyl)morpholin-2-yl]ethanol methanesulfonate

Product 1

HCID 184274891-{2-[2-(3,4-Dichlorophenyl)-4-(3,4,5-trimethoxybenzoyl)morpholin-2-yl]ethyl}-4-phenylpiperidine-4-carboxamideYield 86.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

200 mg (0.36 mmole) of 2-[2-(3,4-dichlorophenyl)-4-(3,4,5-trimethoxybenzoyl)morpholin-2-yl]ethanol methanesulfonate [prepared as described in step (f) above], 105 mg (0.44 mmole) of 4-phenylpiperidine-4-carboxamide hydrochloride, 100 mg (1.19 mmole) of sodium hydrogencarbonate and 100 mg (0.60 mmole) of potassium iodide were suspended in 2 ml of dimethylformamide, and the mixture was then stirred under a stream of nitrogen at 80° C. for 6 hours. The reaction mixture was then poured into water and extracted with ethyl acetate. The extract was then washed with an aqueous solution of sodium thiosulfate, with water and with a saturated aqueous solution of sodium chloride, in that order. The organic extract was then dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The resulting residue was purified by thin-layer chromatography, using a 9:1 by volume mixture of methylene chloride and methanol as the developing solvent and then crystallized from hexane, to give 205 mg (yield 86%) of the title compound.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe extract was then washed with an aqueous solution of sodium thiosulfate, with water and with a saturated aqueous solution of sodium chloride, in that order
  3. extractionThe organic extract
  4. dry with materialwas then dried over anhydrous sodium sulfate
  5. customthe solvent was removed by distillation under reduced pressure
  6. customThe resulting residue was purified by thin-layer chromatography
  7. additionby volume mixture of methylene chloride and methanol as the developing solvent
  8. customcrystallized from hexane

Sources & evidence

ORD record
ord-de27d47fcf9a430e99edebc8e99c7200
Source dataset
uspto-grants-2000_12
Patent number
US06159967

Reaction notes

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