Toluene → [4-(3,5-Dimethylpyridin-2-yl)piperazin-1-yl](4-iodo-2-methylphenyl)methanone

HRID 2411290Notes

Reaction equation

HRID 2411290 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][N:13]([C:16]3[C:21]([CH3:22])=[CH:20][C:19]([CH3:23])=[CH:18][N:17]=3)[CH2:12][CH2:11]2)=[O:9])=[C:4]([CH3:24])[CH:3]=1.[I-:25].[Na+].C1(C)C=CC=CC=1.CNCCNC>[Cu]I.O>[CH3:22][C:21]1[C:16]([N:13]2[CH2:14][CH2:15][N:10]([C:8]([C:5]3[CH:6]=[CH:7][C:2]([I:25])=[CH:3][C:4]=3[CH3:24])=[O:9])[CH2:11][CH2:12]2)=[N:17][CH:18]=[C:19]([CH3:23])[CH:20]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 5238Sodium IodideHCID 8070N,N'-DimethylethylenediamineHCID 58484835(4-Bromo-2-methylphenyl)[4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl]methanone

Product 1

HCID 71252193[4-(3,5-Dimethylpyridin-2-yl)piperazin-1-yl](4-iodo-2-methylphenyl)methanoneYield 59.5%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolvent

Procedure

To a mixture of (4-bromo-2-methylphenyl)[4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl]methanone (842 mg) described in Preparation Example 118, sodium iodide (650 mg) and copper(I) iodide (246 mg) were added toluene (2.2 mL) and N,N′-dimethylethylenediamine (1.62 mL), and the mixture was stirred with heating under reflux for 18 hr under a nitrogen stream. The reaction mixture was cooled, water was added, and the mixture was extracted with ethyl acetate. The solvent was evaporated from the organic layer, and the residue was purified by column chromatography (chloroform:methanol) to give the title compound (562 mg).

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for 18 hr under a nitrogen stream
  3. temperatureThe reaction mixture was cooled
  4. extractionthe mixture was extracted with ethyl acetate
  5. customThe solvent was evaporated from the organic layer
  6. customthe residue was purified by column chromatography (chloroform:methanol)

Sources & evidence

ORD record
ord-3ae8f34ec09d4393a9aee2b17af7bf9d
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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