Iodine → 3-[4-(2-Bromo-5-fluorophenoxy)piperidin-1-yl]isoxazole-5-carboxamide

HRID 561208Notes

Reaction equation

HRID 561208 reaction equation
[Br:1][C:2]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:3]=1[O:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH2:15][CH:14]([C:16]([NH2:18])=[O:17])[O:13][N:12]=2)[CH2:7][CH2:6]1.C([O-])(=O)C.[Na+].II.[O-]S([O-])(=S)=O.[Na+].[Na+]>ClC1C=CC=CC=1.CCOC(C)=O.O>[Br:1][C:2]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:3]=1[O:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:15]=[C:14]([C:16]([NH2:18])=[O:17])[O:13][N:12]=2)[CH2:7][CH2:6]1

Participants

8

Reactant 4

HCID 807IodineHCID 24477Sodium ThiosulfateHCID 517045Sodium AcetateHCID 66696800HCID 66696800, compound

Product 1

HCID 533885293-[4-(2-Bromo-5-fluorophenoxy)piperidin-1-yl]isoxazole-5-carboxamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 7964ChlorobenzeneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred suspension of 3-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-4,5-dihydroisoxazole-5-carboxamide (2.3 g, 5.96 mmol) and sodium acetate (1.3 g, 15.85 mmol) in chlorobenzene (15 mL) was added iodine (2 g, 7.88 mmol). The mixture was heated at reflux temperature for 3 h. After cooling, a solution of Na2S2O3, water and EtOAc were added. The mixture was stirred for 5 min and filtered through celite to remove the insoluble material. The organic layer was then separated, washed with brine, dried (Na2SO4) and concentrated. The residue was triturated with Et2O to give the title compound as light brown powder.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux temperature for 3 h
  3. temperatureAfter cooling
  4. filtrationfiltered through celite
  5. customto remove the insoluble material
  6. customThe organic layer was then separated
  7. washwashed with brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customThe residue was triturated with Et2O

Sources & evidence

ORD record
ord-091711a9d51d4572a203552b8c604b9d
Source dataset
uspto-grants-2011_11
Patent number
US08063224B2

Reaction notes

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