Sulfuric Acid → 2,3-Dichloro-5-iodo-6-methoxypyridine

HRID 1504484Notes

Reaction equation

HRID 1504484 reaction equation
[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[C:4]([O:9][CH3:10])[N:3]=1.C(Cl)Cl.S(=O)(=O)(O)O.[I:19]N1C(=O)CCC1=O>C(OCC)(=O)C.CC(O)=O>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([I:19])=[C:4]([O:9][CH3:10])[N:3]=1

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 6344DichloromethaneHCID 120273N-IodosuccinimideHCID 30192452,3-Dichloro-6-methoxypyridine

Product 1

HCID 1177371982,3-Dichloro-5-iodo-6-methoxypyridineYield 76.1%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

A RBF was charged with 2,3-dichloro-6-methoxypyridine (4.84 g, 27.2 mmol, Accel Pharmtech), DCM (40.0 ml), AcOH (40.0 ml), and sulfuric acid (0.797 ml, 14.95 mmol) to give a clear solution. N-iodosuccinimide (6.12 g, 27.2 mmol) was added in one portion to give a maroon-colored solution. The reaction was stirred for three hours at RT. The mixture was diluted with ethyl acetate, washed with water, washed with 10% aq. sodium thiosulfate, washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (80-g Redi-Sep Gold column, 0-15% Et20/Heptane) to afford 2,3-dichloro-5-iodo-6-methoxypyridine (6.29 g, 20.70 mmol, 76% yield) as a white solid. m/z (ESI) 304.0 (M+H)+.

Workup

  1. customto give a clear solution
  2. customto give a maroon-colored solution
  3. washwashed with water
  4. washwashed with 10% aq. sodium thiosulfate
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography on silica gel (80-g Redi-Sep Gold column, 0-15% Et20/Heptane)

Sources & evidence

ORD record
ord-b0b7adfc7d2341d09fd1d3e83f27cb44
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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