Methanol → Methyl 5-bromo-2-iodobenzoate

HRID 1749375Notes

Reaction equation

HRID 1749375 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([I:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].S(=O)(=O)(O)O.[CH3:17]O>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([I:11])=[C:6]([CH:10]=1)[C:7]([O:9][CH3:17])=[O:8]

Participants

4

Reactant 3

HCID 887MethanolHCID 1118Sulfuric AcidHCID 3029395-Bromo-2-iodobenzoic acid

Product 1

HCID 11078356Methyl 5-bromo-2-iodobenzoateYield 90%

Conditions

Temperature
20 °C

Procedure

Add 5-bromo-2-iodobenzoic acid (1998 g, 6.11 mol) portion wise to a 20° C. solution of sulfuric acid (100 mL) in methanol (13 L). Heat the suspension to reflux for 24 hours, then cool to 20° C. and remove the solvent under reduced pressure. Pour the residue into a 1:1 mixture of methyl-tert-butyl ether and ice water (20 L) and separate the phases. Extract the aqueous phase with methyl-tert-butyl ether (1.5 L), combine the organic phases and wash with aqueous 0.2 M NaOH (5 L), wash with saturated aqueous sodium chloride, dry over sodium sulfate, filter, and evaporate under reduced pressure. Dissolve the crude product in 40-45° C. petroleum ether (10 L), filter through a pad of diatomaceous earth and evaporate under reduced pressure. Dissolve the residue in petroleum ether (5 L) and cool to −50° C., filter the first crop solids, wash the solid with ice cold petroleum ether. Evaporate the mother liquor, redissolve the solid in petroleum ether (1 L), cool to −50° C., and filter a second crop. Combine first and second crops and dry in open air to provide the title compound as a yellow solid (1880 g, 90%).

Workup

  1. temperatureHeat the suspension
  2. temperatureto reflux for 24 hours
  3. customremove the solvent under reduced pressure
  4. additionPour the residue
  5. additioninto a 1:1 mixture of methyl-tert-butyl ether and ice water (20 L)
  6. customseparate the phases
  7. extractionExtract the aqueous phase with methyl-tert-butyl ether (1.5 L)
  8. washwash with aqueous 0.2 M NaOH (5 L)
  9. washwash with saturated aqueous sodium chloride
  10. dry with materialdry over sodium sulfate
  11. filtrationfilter
  12. customevaporate under reduced pressure
  13. dissolutionDissolve the crude product in 40-45° C. petroleum ether (10 L)
  14. filtrationfilter through a pad of diatomaceous earth
  15. customevaporate under reduced pressure
  16. dissolutionDissolve the residue in petroleum ether (5 L)
  17. temperaturecool to −50° C.
  18. filtrationfilter the first crop solids
  19. washwash the solid with ice cold petroleum ether
  20. customEvaporate the mother liquor
  21. dissolutionredissolve the solid in petroleum ether (1 L)
  22. temperaturecool to −50° C.
  23. filtrationfilter a second crop
  24. customCombine first and second crops and dry in open air

Sources & evidence

ORD record
ord-56aee869b68b4fd5b3ff0e627e128ffa
Source dataset
uspto-grants-2015_10
Patent number
US09156824B2

Reaction notes

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