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

Participants

Reaction Conditions

Reaction Steps

A 1.6M solution of butyllithium in hexane (24.4 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 washed with a solution of ethylenediaminetetracetic 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 (CDCl3): 2.4(s,3H), 3.65(s,3H), 7.2(s,4H, 7.35(m,3H), 7.35(m,3H), 7.5(m,1H), 7.8(d,1H).

Provenance & Evidence