Iodine → HCID 54570705, compound

HRID 1816771Notes

Reaction equation

HRID 1816771 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH3:14])=[CH:4][CH:3]=1.[Mg].II.IC(I)C.[CH2:22]([O:29][C:30]([N:32]1[CH2:37][CH2:36][N:35]([C:38]2[CH:43]=[CH:42][C:41]([N:44]3[CH2:49][CH2:48][C:47](=[O:50])[CH2:46][CH2:45]3)=[CH:40][CH:39]=2)[CH2:34][CH2:33]1)=[O:31])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C>[CH2:22]([O:29][C:30]([N:32]1[CH2:37][CH2:36][N:35]([C:38]2[CH:43]=[CH:42][C:41]([N:44]3[CH2:49][CH2:48][C:47]([OH:50])([C:2]4[CH:7]=[CH:6][C:5]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH3:14])=[CH:4][CH:3]=4)[CH2:46][CH2:45]3)=[CH:40][CH:39]=2)[CH2:34][CH2:33]1)=[O:31])[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

9

Reactant 6

HCID 807IodineHCID 25517Ammonium ChlorideHCID 68980DiiodoethaneHCID 5462224MagnesiumHCID 22494784HCID 22494784, compoundHCID 54371450HCID 54371450, compound

Product 1

HCID 54570705HCID 54570705, compoundYield 47.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To the solution of 1-bromo-4-(4-methoxybutoxy)benzene (4.94 g) and magnesium (463 mg) in tetrahydrofuran (50 ml) was added iodine at room temperature. The solution was refluxed for 7.5 hours, during which period diiodoethane was added to the mixture. After cooling to 0° C., 4-[4-(4-oxopiperidin-1-yl)phenyl]piperazine-1-carboxylic acid benzyl ester (4.94 g) in tetrahydrofuran (20 ml) was added dropwise with stirring to the solution. The mixture was stirred at room temperature for 2 hours. The reaction mixture was added to a mixture of ammonium chloride solution and ethyl acetate. The organic layer was taken, washed with brine, sodium hydrogen carbonate solution and brine and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (50:1 dichloromethane-methanol elution) to give 4-[4-[4-hydroxy-4-[4-(4-methoxybutoxy)phenyl]piperidin-1-yl]phenyl]piperazine-1-carboxylic acid benzyl ester (3.42 g).

Workup

  1. additionwas added to the mixture
  2. stirringThe mixture was stirred at room temperature for 2 hours
  3. washwashed with brine, sodium hydrogen carbonate solution and brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationThe magnesium sulfate was filtered off
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography (50:1 dichloromethane-methanol elution)

Sources & evidence

ORD record
ord-1661f82eb00646bbbbdf9e7af5e256f2
Source dataset
uspto-grants-2005_04
Patent number
US06884868B1

Reaction notes

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