4-Bromotoluene → (1,1'-Biphenyl)-2-carboxylic acid, 4'-methyl-, methyl ester

HRID 2254887Notes

Reaction equation

HRID 2254887 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][CH:8]=1.[CH3:14][O:15][C:16](=[O:24])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1I>CCCCCC.O1CCCC1.CCOCC.[Cl-].[Zn+2].[Cl-]>[CH3:13][C:10]1[CH:11]=[CH:12][C:7]([C:18]2[C:17]([C:16]([O:15][CH3:14])=[O:24])=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:8][CH:9]=1

Participants

8

Reactant 3

HCID 78054-BromotolueneHCID 69132Benzoic acid, 2-iodo-, methyl esterHCID 178418339Butyllithium

Product 1

HCID 1393873(1,1'-Biphenyl)-2-carboxylic acid, 4'-methyl-, methyl esterYield 83.5%

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

A 1.6M solution of butyllithium in hexane (24.0 ml) was added dropwise to a stirred solution of 4-bromotoluene (6.0 g) in dry tetrahydrofuran (THF) (50 ml) at -78° C. under an atmosphere of argon. The temperature was maintained at -78° C. for 20 minutes and then a 1M solution of anhydrous zinc chloride in ether (38.6 ml) was added. The solution was kept at -78° C. for 15 minutes, and then tetrakis (triphenylphosphine)palladium (60 mg) in THF (5 ml) was added, followed by methyl-2-iodobenzoate (6.1 g) in THF (10 ml). The solution was allowed to reach ambient temperature over 1 hour, then heated under reflux for 5 hours. The solvent was removed by evaporation and the residue was dissolved in chloroform (150 ml). The solution was washed with a solution of ethylene diaminetetracetic acid (10 g) in water (100 ml) and the aqueous layer was re-extracted with chloroform (100 ml). The combined organic extracts were dried (MgSO4) and the solvent removed by evaporation. The residue was purified by flash chromatography, eluting with ethyl acetate/hexane (1:9 v/v) to give methyl 4'-methylbiphenyl-2-carboxylate (B) as a colourless oil (4.4 g); NMR: 2.4(s,3H), 3.65(s,3H), 7.2(s,4H), 7.35(m,3H), 7.5(m,1H), 7.8(d,1H).

Workup

  1. waitto reach ambient temperature over 1 hour
  2. temperatureheated
  3. temperatureunder reflux for 5 hours
  4. customThe solvent was removed by evaporation
  5. dissolutionthe residue was dissolved in chloroform (150 ml)
  6. washThe solution was washed with a solution of ethylene diaminetetracetic acid (10 g) in water (100 ml)
  7. extractionthe aqueous layer was re-extracted with chloroform (100 ml)
  8. dry with materialThe combined organic extracts were dried (MgSO4)
  9. customthe solvent removed by evaporation
  10. customThe residue was purified by flash chromatography
  11. washeluting with ethyl acetate/hexane (1:9 v/v)

Sources & evidence

ORD record
ord-a974a2dd65614651bc35db9b48a231b9
Source dataset
uspto-grants-1993_08
Patent number
US05236937

Reaction notes

Loading…