Potassium Carbonate → 4-Chloro-1-{[(4-chloro-2-fluorophenyl)methyl]oxy}-2-iodobenzene

HRID 2356617Notes

Reaction equation

HRID 2356617 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([I:9])[CH:3]=1.[Cl:10][C:11]1[CH:18]=[CH:17][C:14]([CH2:15]Br)=[C:13]([F:19])[CH:12]=1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:15][C:14]2[CH:17]=[CH:18][C:11]([Cl:10])=[CH:12][C:13]=2[F:19])=[C:4]([I:9])[CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 6202344-Chloro-2-iodophenolHCID 27365514-Chloro-2-fluorobenzyl bromide

Product 1

HCID 247536874-Chloro-1-{[(4-chloro-2-fluorophenyl)methyl]oxy}-2-iodobenzene

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
22.5 °C

Procedure

To a solution of 4-chloro-2-iodophenol (899 g, 1 eq) and 4-chloro-2-fluorobenzyl bromide (700 g, 1.02 eq) in acetone (8.1 L) was added anhydrous potassium carbonate (926 g). The stirred suspension was then heated to reflux for 30 minutes. 0.12% starting material was observed by HPLC. The product mixture was cooled to 20-25° C. HPLC showed complete consumption of starting material. Inorganic material was then removed by filtration. The residue was washed with acetone (3.6 L) and the combined filtrate and washes were concentrated to 5 vol by atmospheric distillation. Isooctane (4.5 L) was added and reconcentrated to 5 vol by atmospheric distillation. This was repeated once more. The solution was then cooled from 85° C. to 75° C. No precipitation occurred. The batch was then cooled further to 55° C. over 30 minutes, leading to the formation of an immobile suspension. The batch was re-heated to 65° C. which thinned the suspension. The batch was then cooled to 55° C. over 30 minutes. This caused a more controlled precipitation with a mobile suspension.

Workup

  1. temperatureThe stirred suspension was then heated
  2. temperatureto reflux for 30 minutes
  3. customconsumption of starting material
  4. customInorganic material was then removed by filtration
  5. washThe residue was washed with acetone (3.6 L)
  6. concentrationthe combined filtrate and washes were concentrated to 5 vol by atmospheric distillation
  7. additionIsooctane (4.5 L) was added
  8. distillationreconcentrated to 5 vol by atmospheric distillation
  9. temperatureThe solution was then cooled from 85° C. to 75° C
  10. customNo precipitation
  11. temperatureThe batch was then cooled further to 55° C. over 30 minutes
  12. temperatureThe batch was re-heated to 65° C. which
  13. temperatureThe batch was then cooled to 55° C. over 30 minutes
  14. customa more controlled precipitation with a mobile suspension

Sources & evidence

ORD record
ord-6ba10f1450e145b784a4e8be7a519092
Source dataset
uspto-grants-2010_07
Patent number
US07759369B2

Reaction notes

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