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

HRID 2070931Notes

Reaction equation

HRID 2070931 reaction equation
C([N-]C(C)C)(C)C.[Li+].[F:9][C:10]1[CH:15]=[CH:14][C:13]([CH:16]([CH3:18])[CH3:17])=[CH:12][N:11]=1.[I:19]I.O>C1COCC1>[F:9][C:10]1[C:15]([I:19])=[CH:14][C:13]([CH:16]([CH3:18])[CH3:17])=[CH:12][N:11]=1

Participants

6

Reactant 4

HCID 807IodineHCID 962WaterHCID 2724682Lithium diisopropylamideHCID 205879682-Fluoro-5-(1-methylethyl)pyridine

Product 1

HCID 686713802-Fluoro-3-iodo-5-isopropylpyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirring solution of 9.2 mL of LDA (lithium diisopropylamide) (2.0M solution in THF/heptane/ethylbenzene) in 20 mL of THF at −78° C. was added 2-fluoro-5-isopropylpyridine in 40 mL of THF dropwise over a period of 20 min. After 30 min. 4.39 g (17.3 mmol) of iodine in 25 mL of THF was added. After 2 h at −78° C. with the light off, 20 mL of water was added, and the cold bath was removed. Water (80 mL) was added and 9 g of sodium thiosulfate was added in 3 portions. Diethyl ether was added, and the layers were separated. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated. Purification by flash silica gel chromatography (5% Et2O/hexanes) provided 1.83 g of 2-fluoro-3-iodo-5-isopropylpyridine with some impurity.

Workup

  1. customthe cold bath was removed
  2. additionWater (80 mL) was added
  3. addition9 g of sodium thiosulfate was added in 3 portions
  4. additionDiethyl ether was added
  5. customthe layers were separated
  6. washThe organic layer was washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by flash silica gel chromatography (5% Et2O/hexanes)

Sources & evidence

ORD record
ord-de271da41fdf4a51a1c59305da350503
Source dataset
uspto-grants-2012_10
Patent number
US08299267B2

Reaction notes

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