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

HRID 246548Notes

Reaction equation

HRID 246548 reaction equation
C(=O)(O)[O-].[Na+].[F:6][C:7]1[CH:8]=[CH:9][C:10]2[N:11]([CH:13]=[N:14][CH:15]=2)[CH:12]=1.[I:16]I>O.CCO>[F:6][C:7]1[CH:8]=[CH:9][C:10]2[N:11]([CH:13]=[N:14][C:15]=2[I:16])[CH:12]=1

Participants

6

Reactant 3

HCID 807Iodine2×HCID 516892Sodium BicarbonateHCID 717440036-Fluoroimidazo[1,5-A]pyridine

Product 1

HCID 712798256-Fluoro-1-iodoimidazo[1,5-A]pyridine

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a solution of sodium bicarbonate (1.3 g, 15.4 mmol) in water (3.66 mL) was added 6-fluoroimidazo[1,5-a]pyridine (see Example 32, 560 mg, 4.11 mmol) in EtOH (7.31 mL) followed by iodine (1.46 g, 5.76 mmol) at room temperature. After 16 h another 800 mg of iodine was added. After a further 16 h the reaction mixture was quenched with sodium thiosulfate and diluted with ethyl acetate. The organic phase was washed with water and brine then dried (MgSO4), filtered and concentrated in vacuo. Purification by chromatography (silica, ethyl acetate/hexane gradient). The product contained minor impurities and was used without further purification. MS (M+H)+=262.9; 1H NMR (CDCl3) δ: 8.14 (s, 1H), 7.90 (m, 1H), 7.35 (m, 1H), 6.77 (m, 1H).

Workup

  1. customAfter a further 16 h the reaction mixture was quenched with sodium thiosulfate
  2. additiondiluted with ethyl acetate
  3. washThe organic phase was washed with water and brine
  4. dry with materialthen dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by chromatography (silica, ethyl acetate/hexane gradient)
  8. customwas used without further purification

Sources & evidence

ORD record
ord-bcabaadfc7a94575bd9fab0e9ad7a1ee
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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