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

HRID 1699998Notes

Reaction equation

HRID 1699998 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 8028TetrahydrofuranSolvent

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 TBF 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 TBF 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-1674bdfc284b454a90c70b1336059f05
Source dataset
uspto-grants-2002_02
Patent number
US06348624B1

Reaction notes

Loading…