Hydrochloric Acid → 2-(2-Chloro-5-fluoropyrimidin-4-yl)-benzo[b]thiophene-4-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

An aqueous 2N Na2CO3 solution (36 mL) is added dropwise to a stirred solution of (4-carboxybenzo[b]thiophen-2-yl)boronic acid (3.63 g, 18.8 mmol) and 2,4-dichloro-5-fluoropyrimidine (3.00 g, 18.0 mmol) in ethyleneglycol dimethyl ether (50 mL) at room temperature under nitrogen atmosphere. Upon the completion of addition, dichlorobis(triphenylphosphine)palladium(II) (0.22 g, 3% mol) is added in one portion, then the reaction mixture is heated at 100° C. overnight. The mixture is cooled to 10° C., then 37% HCl (10 mL) is added in portions to form a suspension. After filtration and washing with water, the solid is dried under vacuum. The dry solid is suspended in 30 mL of dichloromethane/ethanol (10:1), sonicated, filtered, and dried again to provide 2-(2-chloro-5-fluoropyrimidin-4-yl)-benzo[b]thiophene-4-carboxylic acid (2.95 g, 48% yield).

Provenance & Evidence