Dichloromethane → Biphenyl

Participants

Reaction Conditions

Reaction Steps

To a solution of tert-butyl [(2R)-2-hydroxy-2-phenylethyl][2-(4-iodophenoxy)ethyl]carbamate (350 mg) in toluene (6.0 ml) and ethanol (1.5 ml) was added boric acid (222 mg), [1,1′-bis(diphenylphosphino)ferrocene]-dichlorobispalladium(II), complex with dichloromethane (59 mg), 1,1′-bis(diphenylphosphino)ferrocene (20 mg) and aqueous solution of sodium carbonate (2M, 0.8 ml), and the mixture was stirred at 75° C. for 4 hours under nitrogen. The mixture was partitioned between with ethyl acetate and water. The organic layer was separated, washed with brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane/ethyl acetate=3/1) to give biphenyl product (285 mg). To a solution of the product in methanol (5.0 ml) was added 1N aqueous sodium hydroxide solution (1.5 ml), and the mixture was stirred at 40° C. for 3 hours. The solvent was removed by evaporation, and the aqueous solution was acidified with 1N hydrochloric acid and extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over magnesium sulfate and evaporated under reduced pressure to give a benzoic acid product. To a solution of the product in ethyl acetate (2.0 ml) was added 4N hydrogen chloride in ethyl acetate (2.0 ml), and the mixture was stirred at room temperature for 12 hours. The resultant solid was collected by filtration and dried to give 3-(cyclohexyloxy)-4′-[2-[[(2R)-2-hydroxy-2-phenylethyl]amino]ethoxy]-4-biphenylcarboxylic acid hydrochloride (210 mg).

Provenance & Evidence