Hydrochloric Acid → 2-(4-Hydroxy-2-methyl-phenyl)-benzo[b]thiophene-7-carboxylic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of 2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzo[b]thiophene-7-carboxylic acid ethyl ester (1.04 mmoles; 345.00 mg) in anhydrous DMF (2.5 mL) is added, under nitrogen atmosphere, via syringe pump (3 mL/2 h) to a suspension at 80° C. of 4-bromo-3-methylphenol (1.04 mmoles; 194.23 mg), Cesium carbonate (2.08 mmoles; 683.53 mg), Pd(OAc)2 (103.84 μmoles; 23.55 mg), 1,1′-bis(diphenylphosphino)ferrocene (311 μmoles; 176 mg) in anhydrous DMF (1.6 mL). The mixture is stirred at 80° C. for 1 h and allowed to reach room temperature. The reaction is poured into a mixture of ethyl acetate and HCl (1M), filtered through Celite® and washed with ethyl acetate. The organic layer is separated and the aqueous layer is extracted with ethyl acetate (2×20 mL). The organic layers are combined, washed with water, dried (Na2SO4), filtered and concentrated. The residue is chromatographed (10-40% EtOAc in hexanes) to obtain the title compound (143 mg, 44%) as a white solid. LC-ES/MS m/e 311 (M−1).

Provenance & Evidence