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

Participants

Reaction Conditions

Reaction Steps

An aqueous Na2CO3 solution (2 M, 500 mL) is added dropwise to a stirred solution of (4-carboxy-benzo[b]thiophen-2-yl)boronic acid (56 g, 0.25 mol) and 2,4,6-trichloro-pyrimidine (42.1 g, 0.230 mol) in ethyleneglycol dimethyl ether (620 mL) at room temperature under nitrogen atmosphere. Upon the completion of addition, PdCl2(PPh3)2 (5.31 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 (150 mL) is added in portions to form a suspension. After filtration and washing with water (300 mL×3) the solid is dried under vacuum. Then the solid is suspended in 1 L of dichloromethane/ethanol (10:1) and stirred overnight. After another round of filtration and drying, the first crop of title compound (28.0 g, 38% yield) is obtained. Mother liquor is concentrated and the residue is suspended in acetone (1 mL) and stirred overnight. After filtration, the solid is re-suspended in 200 mL of dichloromethane/ethanol (ethanol) (3:1) and stirred for 2 hours. Additional 5 g of the title compound is obtained after filtration and drying. Overall yield is 44%.

Provenance & Evidence