Ethanol → 3-Chloro-5'-fluoro-2'-methoxy[1,1'-biphenyl]-4-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

4-Bromo-2-chlorobenzoic acid (205 g) and 5-fluoro-2-methoxyphenylboronic acid (161 g) were dissolved in toluene (2 L) and ethanol (2 L) in a 10 L reactor vessel. Sodium carbonate (2 L of a 2 M aqueous solution) was added followed by tetrakis(triphenylphosphine)palladium(0) (15.39 g). The reaction was heated at 75° C. for 16 h. The reaction was diluted with water (2.5 L) and TBME (2 L) and stirred. Further water (0.5 L) was added and the mixture stirred for a further 5 min to complete dissolution of the solids. The aqueous layer was separated, filtered through a Celite pad and cooled to 15° C. The solution was acidified to pH 1 over 1 h by the addition of conc. HCl (532 mL, final pH1). The solid was filtered off and washed with ice cold water (400 ml) to give a tan solid. This was dried for 72 h in a vacuum oven at 45° C. over CaCl2 to give the sub titled product (237 g).

Provenance & Evidence