Potassium Iodide → 2,4-Difluoro-3-iodo-1,5-dimethoxybenzene

HRID 1778653Notes

Reaction equation

HRID 1778653 reaction equation
[F:1][C:2]1[C:8]([O:9][CH3:10])=[CH:7][C:6]([O:11][CH3:12])=[C:5]([F:13])[C:3]=1N.N([O-])=O.[Na+].[I-:18].[K+]>Cl.O>[F:1][C:2]1[C:3]([I:18])=[C:5]([F:13])[C:6]([O:11][CH3:12])=[CH:7][C:8]=1[O:9][CH3:10]

Participants

6

Reactant 3

HCID 4875Potassium IodideHCID 102618922,6-Difluoro-3,5-dimethoxybenzenamineHCID 23668193Sodium Nitrite

Product 1

HCID 867228052,4-Difluoro-3-iodo-1,5-dimethoxybenzeneYield 64.1%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 962WaterSolvent3×

Procedure

To a stirred slurry of 2,6-difluoro-3,5-dimethoxyaniline (6.00 g, 31.7 mmol) in 6.0 M hydrogen chloride in water (54 mL, 324 mmol), a solution of sodium nitrite (2.30 g, 33.3 mmol) in water (12 mL) was added drop-wise over 15 min. at 0° C. After an additional 15 min., the result orange-red slurry was added to a solution of potassium iodide (21.0 g, 126 mmol) in water (30 mL) in small-portion at 0° C. The mixture was then allowed to stir at r.t. for 1 h. The precipitates were collected by filtration, washed with water, and dried under reduced pressure. The filtrate was neutralized with 6 N NaOH to pH˜7, and extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with saturated Na2S2O3 aqueous solution, dried over MgSO4, filtered and concentrated under reduced pressure. The residue combined with the precipitates collected previously was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (gradient: 0-50%) to afford the desired product (6.1 g, 64%). 1H-NMR (300 MHz, CDCl3): 6.68 (t, J=8.0 Hz, 1H), 3.88 (s, 6H).

Workup

  1. filtrationThe precipitates were collected by filtration
  2. washwashed with water
  3. customdried under reduced pressure
  4. extractionextracted with ethyl acetate (3×20 mL)
  5. washThe combined organic layers were washed with saturated Na2S2O3 aqueous solution
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customcollected previously
  10. customwas purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (gradient: 0-50%)

Sources & evidence

ORD record
ord-51a7cc1f7d3441fbb86e44e0453ca7ab
Source dataset
uspto-grants-2016_02
Patent number
US09266892B2

Reaction notes

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