Methyl iodide → 3-Bromo-2,6-difluorotoluene

HRID 1455488Notes

Reaction equation

HRID 1455488 reaction equation
[CH2:1]([Li])CCC.[Br:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][C:8]=1[F:14].IC>C1COCC1>[CH3:1][C:9]1[C:8]([F:14])=[C:7]([Br:6])[CH:12]=[CH:11][C:10]=1[F:13]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 676741-Bromo-2,4-difluorobenzeneHCID 178418339Butyllithium

Product 1

HCID 112872263-Bromo-2,6-difluorotoluene

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Diisoproplylamine (11.9 ml, 85 mmol) is dissolved in 50 ml of anhydrous THF and cooled in a dry ice/acetone bath. n-Butyllithium (34 ml of a 2.5 M solution in hexanes, 85 mmol) is added dropwise. After 15 minutes, a solution of 1-bromo-2,4-difluorobenzene (16 g, 83 mmol) in 8 ml of THF is added at a rate to keep the temperature below −65° C. The reaction is stirred for 2.5 hours then a solution of iodomethane (10.3 ml, 166 mmol) in 8 ml of THF is added to the reaction. The ice bath is removed and the reaction is allowed to warm to room temperature. After 2 hours the reaction is quenched with water and 1N HCl. The aqueous layer is extracted twice with ether. The combined organics are washed with brine and dried over Na2SO4. Removal of the solvent affords the desired product.

Workup

  1. temperaturecooled in a dry ice/acetone bath
  2. customthe temperature below −65° C
  3. customThe ice bath is removed
  4. customAfter 2 hours the reaction is quenched with water and 1N HCl
  5. extractionThe aqueous layer is extracted twice with ether
  6. washThe combined organics are washed with brine
  7. dry with materialdried over Na2SO4
  8. customRemoval of the solvent

Sources & evidence

ORD record
ord-a73f5e33bdba43b78be764b75cb4413b
Source dataset
uspto-grants-2009_01
Patent number
US07482454B2

Reaction notes

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