Application of 3-methylbenzofuran-2-carbonyl chloride_Kain Industrial Additive

Overview^[1]

3-Methylbenzofuran-2-carbonyl chloride can be used as a pharmaceutical synthesis intermediate to synthesize other active compounds with this core structure.

Preparation^[1]

3-Methylbenzofuran-2-carbonyl chloride Preparation: Into a 50-mL 3-neck round-bottom flask purged and maintained with an inert atmosphere of nitrogen: 3-methyl in DCM (10 mL) – A solution of 1-benzofuran-2-carboxylic acid (500 mg, 2.84 mmol) and DMF (0.1 mL), then the solution was cooled to 0°C and oxalyl chloride (470 mg, 3.70 mmol) was added dropwise with stirring. The reaction was stirred at 0°C for 2 h and then concentrated under reduced pressure to provide 500 mg (91%) of the title compound, 3-methylbenzofuran-2-carbonyl chloride, as an off-white solid.

Apply^[1]

3-Methylbenzofuran-2-carbonyl chloride can be used as a pharmaceutical synthesis intermediate to synthesize other active compounds with this core structure, such as the preparation of 6-(benzyloxy)-3-methyl-2 -(3-Methyl-1-benzofuran-2-amino)benzoic acid. Into a 250-mL round-bottomed flask purged and maintained with an inert atmosphere of nitrogen: 2-amino-6-( in THF/H₂O (2/1, 93 mL) Benzyloxy)-3-methylbenzoic acid solution (687 mg, 2.67 mmol, as prepared in step A), then add Na₂CO₃ (809.8 mg , 7.64 mmol) and the mixture was cooled to 0°C. A solution of 3-methylbenzofuran-2-carbonyl chloride (494 mg, 2.54 mmol, as prepared in the previous step) in THF (10 mL) was added dropwise, and the resulting solution was stirred at room temperature for 30 min. The reaction was diluted with H₂O and the solid was isolated by filtration to provide 498 mg (47%) of the title compound 6-(benzyloxy)-3-methyl-2-(3) as a gray solid -Methyl-1-benzofuran-2-amino)benzoic acid. Mass spectrum (LCMS, positive ESI): for C₂₅H₂₂NO₅⁺: 416.2(M+H ) calculated; experimental value: 416.1.

Main reference materials

[1](CN108430994) Compounds, compositions and methods for modulating CFTR