Potassium Iodide → 1-(Cyclopropyloxy)-2-iodo-4-(trifluoromethoxy)benzene

HRID 1166076Notes

Reaction equation

HRID 1166076 reaction equation
N([O-])=O.[Na+].[CH:5]1([O:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:18])[F:17])=[CH:11][C:10]=2N)[CH2:7][CH2:6]1.[I-:21].[K+]>O.Cl>[CH:5]1([O:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:18])[F:17])=[CH:11][C:10]=2[I:21])[CH2:7][CH2:6]1

Participants

6

Reactant 3

HCID 4875Potassium IodideHCID 215840842-Cyclopropoxy-5-(trifluoromethoxy)benzeneamineHCID 23668193Sodium Nitrite

Product 1

HCID 117596921-(Cyclopropyloxy)-2-iodo-4-(trifluoromethoxy)benzeneYield 88%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 962WaterSolvent2×

Conditions

Temperature
0 °C

Procedure

An ice-cooled solution of sodium nitrite (3.55 g, 51 mmol) in water (10 mL) was added dropwise to a stirred, cooled (0° C.) solution of 2-cyclopropoxy-5-(trifluoromethoxy)benzeneamine (Description 7, 4.8 g, 20.6 mmol) in aqueous hydrochloric acid (5M, 300 mL), maintaining the internal temperature at 0° C. The mixture was stirred at 0° C. for 30 min., then potassium iodide (8.55 g, 51.5 mmol) in water (10 mL) was added dropwise, maintaining the internal temperature at 0° C. The mixture was stirred at 0° C. for 30 min., then allowed to warm up to room temperature and stirred until nitrogen evolution ceased. The mixture was extracted with ether, the organic fraction was washed with aqueous sodium thiosulfate (10%), dried (MgSO4), and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with hexane/Et2O (98:2 increasing to 95:5), to give the title compound as a colourless oil (6.23 g, 88%). 1H NMR (360 MHz, CDCl3) δ 7.62 (1H, d, J=2.4 Hz), 7.20 (1H, dd, J=9.1, 2.4 Hz), 7.15 (1H, d, J=9.1 Hz), 3.80 (1H, m), and 0.83 (4H, m).

Workup

  1. additionwas added dropwise to a stirred
  2. temperaturemaintaining the internal temperature at 0° C
  3. stirringThe mixture was stirred at 0° C. for 30 min.
  4. temperatureto warm up to room temperature
  5. stirringstirred until nitrogen evolution
  6. extractionThe mixture was extracted with ether
  7. washthe organic fraction was washed with aqueous sodium thiosulfate (10%)
  8. dry with materialdried (MgSO4)
  9. customthe solvent was evaporated under reduced pressure
  10. customThe residue was purified by flash column chromatography on silica gel
  11. washeluting with hexane/Et2O (98:2 increasing to 95:5)

Sources & evidence

ORD record
ord-e296a5544f674f189bf6857e57276ec9
Source dataset
uspto-grants-2003_09
Patent number
US06613765B1

Reaction notes

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