4-Bromotoluene → 4'-Methyl-biphenyl-3-carboxylic acid ethyl ester

HRID 1077828

Reaction equation

HRID 1077828 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([CH3:9])=[CH:5][CH:4]=1.CC(C[AlH]CC(C)C)C.I[C:20]1[CH:21]=[C:22]([CH:28]=[CH:29][CH:30]=1)[C:23]([O:25][CH2:26][CH3:27])=[O:24]>O1CCCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:9][C:6]1[CH:7]=[CH:8][C:3]([C:20]2[CH:30]=[CH:29][CH:28]=[C:22]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:21]=2)=[CH:4][CH:5]=1

Participants

7

Reactant 4

HCID 78054-BromotolueneHCID 14487Diisobutylaluminum hydrideHCID 143542Ethyl 3-iodobenzoateHCID 5462224Magnesium2×

Product 1

HCID 107287544'-Methyl-biphenyl-3-carboxylic acid ethyl esterYield 59.2%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

Magnesium (1.6 g) and p-bromotoluene (10.26 g) in 60 ml of tetrahydrofuran were stirred and warmed until the reaction commenced. When the exothermic reaction had finished, the mixture was refluxed overnight. In a separate flask, 4 ml of DIBAL (1M in toluene) was added to a suspension of bis(triphenylphosphine)palladium(II) chloride (1.4 g) in 100 ml of tetrahydrofuran, followed by ethyl 3-iodobenzoate (11.04 g). To this mixture, the magnesium reagent prepared above was added dropwise, causing an exothermic reaction. The reaction mixture was stirred overnight at room temperature, and then quenched by addition of dilute hydrochloric acid. The mixture was extracted with ether, and the organic layer washed with water, and then saturated brine. The organic layer was separated, dried over sodium sulfate, the solvent evaporated under reduced pressure, and the residue chromatographed on silica gel, eluting with 5% ethyl acetate in heptane, to yield 5.69 g of ethyl 4'-methylbiphenyl-3-carboxylate, a compound of Formula (17), as a pale yellow oil.

Workup

  1. temperaturewarmed until the reaction commenced
  2. customWhen the exothermic reaction
  3. temperaturethe mixture was refluxed overnight
  4. additionabove was added dropwise
  5. customan exothermic reaction
  6. customquenched by addition of dilute hydrochloric acid
  7. extractionThe mixture was extracted with ether
  8. washthe organic layer washed with water
  9. customThe organic layer was separated
  10. dry with materialdried over sodium sulfate
  11. customthe solvent evaporated under reduced pressure
  12. customthe residue chromatographed on silica gel
  13. washeluting with 5% ethyl acetate in heptane

Sources & evidence

ORD record
ord-35c48f52b06d4ec986257d5697e09ada
Source dataset
uspto-grants-1996_08
Patent number
US05545645

Linked notes

Loading…