Sodium Iodide → 1-benzyl-3-{3-[4-(4-fluorophenyl)piperidin-1-yl]propyl}-5-methyl-1H-pyrimidine-2,4-dione

HRID 1977230Notes

Reaction equation

HRID 1977230 reaction equation
Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:5][CH:4]=1.[CH2:15]([N:22]1[CH:27]=[C:26]([CH3:28])[C:25](=[O:29])[N:24]([CH2:30][CH2:31][CH2:32]Br)[C:23]1=[O:34])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[I-].[Na+].C(=O)([O-])[O-].[K+].[K+]>C(#N)C.ClCCl.O>[CH2:15]([N:22]1[CH:27]=[C:26]([CH3:28])[C:25](=[O:29])[N:24]([CH2:30][CH2:31][CH2:32][N:12]2[CH2:11][CH2:10][CH:9]([C:6]3[CH:7]=[CH:8][C:3]([F:2])=[CH:4][CH:5]=3)[CH2:14][CH2:13]2)[C:23]1=[O:34])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

8

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 155501521-benzyl-3-(3-bromopropyl)-5-methyl-1H-pyrimidine-2,4-dioneHCID 218981684-(4-Fluoro-phenyl)-piperidine hydrochloride

Product 1

HCID 99546541-benzyl-3-{3-[4-(4-fluorophenyl)piperidin-1-yl]propyl}-5-methyl-1H-pyrimidine-2,4-dioneYield 61%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

A suspension of 4-(4-fluorophenyl)piperidine hydrochloride (105 mg, 0.49 mmol) and 1-benzyl-3-(3-bromopropyl)-5-methyl-1H-pyrimidine-2,4-dione (164 mg, 0.49 mmol) in 20 mL acetonitrile was treated with sodium iodide (134 mg, 0.97 mmol) and potassium carbonate (100 mg, 0.73 mmol) and the reaction was heated at reflux for 16 h. The mixture was cooled to ambient temperature and poured into a separatory finnel containing water (100 mL) and dichloromethane (100 mL) and the layers separated. The aqueous layer was extracted with dichloromethane (2×100 mL) and the combined organics dried with magnesium sulfate, filtered and concentrated in vacuo to provide an oil. This crude material was purified by pressurized silica gel chromatography (5% methanol in ethyl acetate) to give 1-benzyl-3-{3-[4-(4-fluorophenyl)piperidin-1-yl]propyl}-5-methyl-1H-pyrimidine-2,4-dione (130 mg, 61%). The hydrochloride salt was prepared by conventional methods to provide a white solid.

Workup

  1. temperaturethe reaction was heated
  2. temperatureat reflux for 16 h
  3. additionpoured into a separatory finnel
  4. customthe layers separated
  5. extractionThe aqueous layer was extracted with dichloromethane (2×100 mL)
  6. dry with materialthe combined organics dried with magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto provide an oil
  10. customThis crude material was purified by pressurized silica gel chromatography (5% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-2b835fe6aafb4999a9e7da678f052590
Source dataset
uspto-grants-2001_05
Patent number
US06232318B1

Reaction notes

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