Sodium Iodide → N-(3-{1-[4,4-bis(4-fluorophenyl)butyl]-4-piperidinyl}-4-methylphenyl)-2-methylpropanamide

HRID 1832265Notes

Reaction equation

HRID 1832265 reaction equation
[CH3:1][CH:2]([CH3:19])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([CH:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)[CH:7]=1)=[O:4].Cl[CH2:21][CH2:22][CH2:23][CH:24]([C:32]1[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=1)[C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1.[Na+].[I-].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O>[F:31][C:28]1[CH:27]=[CH:26][C:25]([CH:24]([C:32]2[CH:33]=[CH:34][C:35]([F:38])=[CH:36][CH:37]=2)[CH2:23][CH2:22][CH2:21][N:16]2[CH2:17][CH2:18][CH:13]([C:8]3[CH:7]=[C:6]([NH:5][C:3](=[O:4])[CH:2]([CH3:19])[CH3:1])[CH:11]=[CH:10][C:9]=3[CH3:12])[CH2:14][CH2:15]2)=[CH:30][CH:29]=1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 768201,1'-(4-Chlorobutylidene)bis(4-fluorobenzene)HCID 167572542-Methyl-N-[4-methyl-3-(4-piperidinyl)phenyl]propanamide

Product 1

HCID 22048974N-(3-{1-[4,4-bis(4-fluorophenyl)butyl]-4-piperidinyl}-4-methylphenyl)-2-methylpropanamideYield 38.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 2-methyl-N-[4-methyl-3-(4-piperidinyl)phenyl]propanamide (49.0 mg, 0.190 mmol), 1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene (58.0 mg, 0.210 mmol), NaI (42.0 mg, 0.280 mmol) and K2CO3 (52.0 mg, 0.380 mmol) in DMF (10.0 mL) was heated at 95° C. overnight. The mixture was diluted with water (20 mL) and the aqueous layer was extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine, dried over MgSO4 and concentrated in vacuo. The crude product was purified by flash chromatography [5% NH3 (2.0 M in MeOH) in CH2Cl2] to afford N-(3-{1-[4,4-bis(4-fluorophenyl)butyl]-4-piperidinyl}-4-methylphenyl)-2-methylpropanamide (37.0 mg, 38.0%).

Workup

  1. extractionthe aqueous layer was extracted with EtOAc (3×20 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by flash chromatography [5% NH3 (2.0 M in MeOH) in CH2Cl2]

Sources & evidence

ORD record
ord-4b1316b5cdb04629b31fff7da2225fc8
Source dataset
uspto-grants-2006_06
Patent number
US07067534B1

Reaction notes

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