Iodine → 5-Cyclopropyl-2-fluoro-3-iodopyridine

HRID 561022Notes

Reaction equation

HRID 561022 reaction equation
[CH:1]1([C:4]2[CH:5]=[CH:6][C:7]([F:10])=[N:8][CH:9]=2)[CH2:3][CH2:2]1.C([N-]C(C)C)(C)C.[Li+].[I:19]I.S([O-])([O-])(=O)=S.[Na+].[Na+]>C1COCC1.O>[CH:1]1([C:4]2[CH:5]=[C:6]([I:19])[C:7]([F:10])=[N:8][CH:9]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 807IodineHCID 24477Sodium ThiosulfateHCID 2724682Lithium diisopropylamideHCID 576908315-Cyclopropyl-2-fluoropyridine

Product 1

HCID 667383455-Cyclopropyl-2-fluoro-3-iodopyridineYield 68%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Cool a solution of 5-cyclopropyl-2-fluoro-pyridine (1.3 g, 9.5 mmol) in THF (20 mL) to −75° C. in a dry ice-acetone bath under nitrogen. Add lithium diisopropylamide (2 M in THF, 6 mL, 12 mmol) over a period of 30 min. Stir the mixture for an additional 3 hours. Add iodine (2.9 g, 11.4 mmol, dissolved in 50 mL of THF) and stir the mixture for 2 hours. Add water (100 mL) and allow the temperature to rise to room temperature over 1 hour while stirring. Treat the mixture with saturated aqueous sodium thiosulfate solution (50 mL). Extract the solution with ether. Concentrate the solution in vacuo to brown oil. Purify by column chromatography (hexane to 20% ethyl acetate in hexane) to afford the title compound (1.7 g, 68%) as a yellow oil. 1H NMR (400 MHz-CDCl3) δ 8.03 (dd, J=3, 8 Hz, 1H), 7.99 (s, 1H), 0.91-1.00 (m, 2H), 0.71-0.78 (m, 2H).

Workup

  1. waitto rise to room temperature over 1 hour
  2. stirringwhile stirring
  3. extractionExtract the solution with ether
  4. concentrationConcentrate the solution in vacuo to brown oil
  5. customPurify by column chromatography (hexane to 20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-5670428a1cc94c55bd90959a66a6f344
Source dataset
uspto-grants-2011_11
Patent number
US08063212B2

Reaction notes

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