Iodine → 2,6-Difluoro-3-iodopyridine

HRID 1253561Notes

Reaction equation

HRID 1253561 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[N:15]=1.[I:21]I.S([O-])([O-])=O.[Na+].[Na+]>O1CCCC1.C(OCC)C>[F:13][C:14]1[C:19]([I:21])=[CH:18][CH:17]=[C:16]([F:20])[N:15]=1

Participants

8

Reactant 5

HCID 807IodineHCID 7912DiisopropylamineHCID 24437Sodium SulfiteHCID 739342,6-DifluoropyridineHCID 178418339Butyllithium

Product 1

HCID 197684332,6-Difluoro-3-iodopyridine

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of butyllithium (38.8 ml, 97 mmol) in tetrahydrofuran (194 ml) at −78° C. was added diisopropylamine (13.8 ml, 97 mmol) dropwise. After 15 minutes at −78° C., 2,6-difluoropyridine (8.8 ml, 97 mmol) was added slowly. After 1 hour slowly, a solution of iodine (24.6 g, 97 mmol) in tetrahydrofuran (50 ml) was carefully added, keeping the internal temperature at −78° C. Sodium sulfite (3.0 g, 24 mmol) was added and the temperature was allowed to gradually increase to ambient temperature. The reaction mixture was diluted with ethyl ether, washed with water, then dried over magnesium sulfate, filtered, and concentrated. The residue was purified by column chromatography on silica gel, eluting (ethyl acetate/isohexane gradient) to give 2,6-difluoro-3-iodopyridine.

Workup

  1. waitAfter 1 hour slowly
  2. customat −78° C
  3. washwashed with water
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica gel
  8. washeluting (ethyl acetate/isohexane gradient)

Sources & evidence

ORD record
ord-6f9d7a33b87a461b8ecf244f41946302
Source dataset
uspto-grants-2013_06
Patent number
US08455477B2

Reaction notes

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