23967-57-9

4-Chlorobenzo[b]thiophene-2-carboxylic Acid is an intermediate used to prepare histone deacetylase inhibitors.

General procedure for the synthesis of 4-chlorobenzo[b]thiophene-2-carboxylic acid from methyl 4-chlorobenzo[b]thiophene-2-carboxylate: Methyl 4-chlorobenzo[b]thiophene-2-carboxylate (1.0 g, 4.44 mmol) and LiOH-H2O (0.56 g, 13.3 mmol) were mixed in a solvent mixture of methanol (30 mL) and water (10 mL), and the reaction was carried out at room temperature. The reaction was carried out overnight. After completion of the reaction, the reaction mixture was concentrated under vacuum and the residue was diluted with ice water (20 mL). The aqueous phase was acidified with dilute hydrochloric acid solution to pH=1. The acidified mixture was extracted with ethyl acetate (15 mL x 3). The organic layers were combined, washed with saturated brine, dried over anhydrous Na2SO4, and the solvent was evaporated under vacuum to give 4-chlorobenzo[b]thiophene-2-carboxylic acid as a white solid (0.94 g, 100% yield).1H NMR (400 MHz, CDCl3) δ 8.10-8.02 (m, 2H), 7.61-7.51 (m, 2H).

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