Iodine → 6-Chloro-1-iodoimidazo[1,5-A]pyridine

HRID 246546Notes

Reaction equation

HRID 246546 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[N:9][CH:10]=2)[CH:7]=1.C(=O)(O)[O-].[Na+].[I:16]I>CCO.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[N:9][C:10]=2[I:16])[CH:7]=1

Participants

6

Reactant 3

HCID 807IodineHCID 516892Sodium BicarbonateHCID 717439986-Chloroimidazo[1,5-A]pyridine

Product 1

HCID 712796546-Chloro-1-iodoimidazo[1,5-A]pyridineYield 36%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a solution of 6-chloroimidazo[1,5-a]pyridine (417 mg, 2.73 mmol) in EtOH (5 mL) and water (2.4 mL) was added sodium bicarbonate (861 mg, 10.2 mmol) and iodine (832 mg, 3.28 mmol) and the mixture stirred at room temperature under N2. After 16 h the reaction mixture was quenched with sodium thiosulfate, then extracted into ethyl acetate. The organic layer was washed with water and brine, dried (MgSO4), filtered, and concentrated. Purification of the filtrate by chromatography (silica, 20-60% ethyl acetate/hexanes) gave 6-chloro-1-iodoimidazo[1,5-a]pyridine (271 mg, 973 μmol, 36%) as a brown solid. MS (M+H)+=278.8; 1H NMR (CDCl3) δ: 8.10 (s, 1H), 8.0 (m, 1H), 7.30 (d, J=9.5 Hz, 1H), 6.76 (9.5 m, 1H).

Workup

  1. customAfter 16 h the reaction mixture was quenched with sodium thiosulfate
  2. extractionextracted into ethyl acetate
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification of the filtrate by chromatography (silica, 20-60% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-bc47ca8f25864824ae7f6f5cf1c79dfb
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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