Hydrochloric Acid → 1-Chloro-4-fluoro-2-iodo-5-methoxybenzene

HRID 1831490Notes

Reaction equation

HRID 1831490 reaction equation
[Cl:1][C:2]1[CH:8]=[C:7]([O:9][CH3:10])[C:6]([F:11])=[CH:5][C:3]=1N.Cl.NC1C=CC=CC=1.N([O-])=O.[Na+].[I-:24].[K+]>O.ClCCl>[Cl:1][C:2]1[CH:8]=[C:7]([O:9][CH3:10])[C:6]([F:11])=[CH:5][C:3]=1[I:24]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 4875Potassium IodideHCID 6115AnilineHCID 220520702-Chloro-5-fluoro-4-methoxyanilineHCID 23668193Sodium Nitrite

Product 1

HCID 220521261-Chloro-4-fluoro-2-iodo-5-methoxybenzeneYield 92%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

2-Chloro-5-fluoro-4-methoxyaniline (14.0 g, 79.7 mmol) was cooled to 0° C. and conc. HCl (40 mL) was added over 20 min. The suspension was heated to 55° C. until the aniline was completely dissolved, then cooled back to 0° C. A solution of sodium nitrite (6.1 g, 87.7 mmol) in water (15 mL) was added dropwise over 15 min. After complete addition the mixture was stirred at 0° C. for 30 min. Hexanes (24 mL) and dichloromethane (24 mL) were added followed by a solution of potassium iodide (26.5 g, 159.4 mmol) in water (25 mL) which was added dropwise over 30 min. After stirring at 0° C. for 4 h dichloromethane (50 mL) was added and the reaction quenched with sat. aq. NaHSO3. The solution was extracted with dichloromethane. The organic layers were washed with brine, dried (Na2SO4), filtered and concentrated in vacuo to give 21 g (92%) of 1-chloro-4-fluoro-2-iodo-5-methoxy-benzene: Crude 1H NMR (400 MHz, CDCl3): δ 7.48 (d, J=10.3 Hz, 1H), 7.04 (d, J=7.8 Hz, 1H), 3.86 (s, 3H). The crude material was pure enough to carry on to the next step.

Workup

  1. dissolutionwas completely dissolved
  2. additionAfter complete addition the mixture
  3. additionwas added dropwise over 30 min
  4. additionwas added
  5. customthe reaction quenched with sat. aq. NaHSO3
  6. extractionThe solution was extracted with dichloromethane
  7. washThe organic layers were washed with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-82f409c4e429430e879469af86c970ac
Source dataset
uspto-grants-2006_06
Patent number
US07067658B2

Reaction notes

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