1-Bromo-4-iodobenzene → 4-[1-(4-Bromophenyl)piperidin-4-yloxy]pyridine

HRID 1510045Notes

Reaction equation

HRID 1510045 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][CH:3]=1.[NH:9]1[CH2:14][CH2:13][CH:12]([O:15][C:16]2[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=2)[CH2:11][CH2:10]1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)(=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:19]2[CH2:20][CH2:21][CH:16]([O:15][C:12]3[CH:13]=[CH:14][N:9]=[CH:10][CH:11]=3)[CH2:17][CH2:18]2)=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 115221-Bromo-4-iodobenzeneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 51521554-(Piperidin-4-yloxy)pyridineHCID 23676156Sodium t-butoxide

Product 1

HCID 668633164-[1-(4-Bromophenyl)piperidin-4-yloxy]pyridineYield 50.9%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

2 g of 1-bromo-4-iodobenzene and 1.386 g of 4-(piperidin-4-yloxy)pyridine are placed in 35 ml of toluene and then 0.324 g of tris(dibenzylideneacetone)dipalladium(0), 0.245 g of 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene and 1.019 g of sodium tert-butoxide are added. The reaction medium is heated at 110° C. for 18 h. Ethyl acetate is subsequently added and the mixture is washed twice with water and once with a saturated aqueous sodium chloride solution. The organic phase is dried over magnesium sulphate and concentrated under reduced pressure. The crude product obtained is chromatographed on silica gel, elution being carried out with a gradient of a dichloromethane/methanol (99/1 to 98/2) mixture. 1.2 g of 4-[1-(4-bromophenyl)piperidin-4-yloxy]pyridine are obtained.

Workup

  1. washthe mixture is washed twice with water and once with a saturated aqueous sodium chloride solution
  2. dry with materialThe organic phase is dried over magnesium sulphate
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product obtained
  5. customis chromatographed on silica gel, elution

Sources & evidence

ORD record
ord-5ab70dd6b78b42018b1fb625cdcd2184
Source dataset
uspto-grants-2012_07
Patent number
US08211892B2

Reaction notes

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