Iodine → 2-Fluoro-3-iodo-5-methylpyridine

HRID 2253326Notes

Reaction equation

HRID 2253326 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[F:13][C:14]1[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][N:15]=1.[I:21]I>C1COCC1>[F:13][C:14]1[C:19]([I:21])=[CH:18][C:17]([CH3:20])=[CH:16][N:15]=1

Participants

6

Reactant 4

HCID 807IodineHCID 7912DiisopropylamineHCID 27746352-Fluoro-5-methylpyridineHCID 178418339Butyllithium

Product 1

HCID 102432202-Fluoro-3-iodo-5-methylpyridineYield 61.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of diisopropylamine (7.0 mL, 50.0 mmol) in THF (100 mL) at −78° C. was treated with 2.5M n-butyllithium in hexanes (20 mL, 50.0 mmol), stirred for 15 minutes, treated dropwise with a solution of 2-fluoro-5-methylpyridine (5.55 g, 50.0 mmol) in THF (20.0 mL), stirred for 4 hours, treated slowly with a solution of iodine (12.7 g. 50.0 mmol) in THF (50 mL), quenched with water, and extracted with diethyl ether. The combined extracts were washed sequentially with Na2S2O3, water, and brine, dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 6:1 hexanes/diethyl ether to provide 7.24 g (61%) of 2-fluoro-3-iodo-5-methylpyridine.

Workup

  1. stirringstirred for 4 hours
  2. customquenched with water
  3. extractionextracted with diethyl ether
  4. washThe combined extracts were washed sequentially with Na2S2O3, water, and brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe concentrate was purified by flash column chromatography on silica gel with 6:1 hexanes/diethyl ether

Sources & evidence

ORD record
ord-4c5a6cc008454812a2f1c8614bd22921
Source dataset
uspto-grants-2008_01
Patent number
US07323570B2

Reaction notes

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