Sodium Iodide → N-(3-{1-[(3R)-3-(3,4-Dimethoxyphenoxy)-3-Phenylpropyl]-4-Piperidinyl}Phenyl)-2-Methylpropanamide

HRID 2087167Notes

Reaction equation

HRID 2087167 reaction equation
C(=O)([O-])[O-].[K+].[K+].[I-].[Na+].[CH3:9][CH:10]([CH3:26])[C:11]([NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)[CH:15]=1)=[O:12].Cl[CH2:28][CH2:29][C@@H:30]([O:37][C:38]1[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[C:40]([O:46][CH3:47])[CH:39]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>CN(C=O)C.O>[CH3:47][O:46][C:40]1[CH:39]=[C:38]([CH:43]=[CH:42][C:41]=1[O:44][CH3:45])[O:37][C@@H:30]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH2:29][CH2:28][N:23]1[CH2:24][CH2:25][CH:20]([C:16]2[CH:15]=[C:14]([NH:13][C:11](=[O:12])[CH:10]([CH3:26])[CH3:9])[CH:19]=[CH:18][CH:17]=2)[CH2:21][CH2:22]1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 167572552-methyl-N-[3-(4-piperidyl)phenyl]propanamideHCID 600786704-([(1R)-3-chloro-1-phenylpropyl]oxy)-1,2-dimethoxybenzene

Product 1

HCID 10279479N-(3-{1-[(3R)-3-(3,4-Dimethoxyphenoxy)-3-Phenylpropyl]-4-Piperidinyl}Phenyl)-2-MethylpropanamideYield 90.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of potassium carbonate (321 mg, 2.32 mmol), sodium iodide (522 mg, 3.48 mmol), 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide (570 mg, 2.32 mmol) and 4-{[(1R)-3-chloro-1-phenylpropyl]oxy}-1,2-dimethoxybenzene (712 mg, 2.32 mmol) in DMF (5.0 mL) was stirred at 100° C. for 3 hrs, at which time TLC indicated that the reaction was complete. The reaction mixture was poured into water (50 mL) and the aqueous layer was extracted with methylene chloride (3×30 mL). The combined organic extracts were washed with brine (30 mL), dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by Prep-TLC plates [2.5% of NH3 (2.0 M in methanol) in CHCl3] to afford the product (970 mg, 90.1%) as a thick oil.

Workup

  1. extractionthe aqueous layer was extracted with methylene chloride (3×30 mL)
  2. washThe combined organic extracts were washed with brine (30 mL)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was purified by Prep-TLC plates [2.5% of NH3 (2.0 M in methanol) in CHCl3]

Sources & evidence

ORD record
ord-8fb4515984af4dd1be0f47c95a7b87c4
Source dataset
uspto-grants-2004_04
Patent number
US06727264B1

Reaction notes

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