Boronic acid, B-(5-chloro-2-benzofuranyl)-

Uses

5-Chlorobenzofuran-2-boronic Acid acts as a reagent in the synthesis of (ary)benzofuran containing natural products. Also acts as a reagent for the preparation of quinoxaline compounds for the inhibition of PASK useful in treating diseases.

Synthesis

General Steps: Step A: Preparation of 5-chlorobenzofuran Synthesis of 5-chlorobenzofuran by heating 4-chlorophenoxyacetaldehyde dimethyl acetal in polyphosphoric acid; Yield: 73%. Step B: Synthesis of 5-chlorobenzofuran-2-boronic acid To a solution of 8.8 g (57.7 mmol) of 5-chlorobenzofuran in 250 ml of anhydrous ether was added 7.32 g (63.0 mmol) of tetramethylethylenediamine (TMEDA). The solution was cooled below -60°C under argon protection and 37.5 ml of 1.6 M butyl lithium hexane solution was added slowly and dropwise. The reaction mixture was gradually warmed to -10°C over 45 minutes and stirring was continued at this temperature for 30 minutes. The mixture was again cooled to below -60°C, followed by dropwise addition of 35.7 g (190 mmol) of triisopropyl borate. After the reaction mixture was warmed to room temperature, the reaction was quenched with 70 ml of 2N hydrochloric acid and stirred for 1 hour. The organic layer was separated and washed sequentially with 30 ml of 2N hydrochloric acid three times and water twice, then extracted with 2N sodium hydroxide solution. The basic aqueous layer was adjusted to pH 5 and extracted with tert-butyl methyl ether. All organic layers were combined, dried with sodium sulfate and concentrated in vacuum to give light yellow crystalline 5-chlorobenzofuran-2-boronic acid, which can be used in the next reaction without further purification. Yield: 9.4 g (83%); MS 196 (M+).

References

[1] Patent: US6410562, 2002, B1