Sulfuric Acid → 5-(7-Methoxybenzo(b)furan-2-yl)-3-methylisoxazole

Thionyl chloride (10 ml) was added dropwise to methanol (100 ml) with stirring under ice-cooling. 7-Methoxybenzo(b)furan-2-carboxylic acid (10 g) was successively added, and the mixture was refluxed under heating for 1 hr. After cooling, the solvent was evaporated under reduced pressure and the precipitated yellow crystals were collected by filtration to give methyl 7-methoxybenzo(b)furan-2-carboxylate (11.2 g). This was used in the next reaction without purification. Acetone oxime (4.8 g) was dissolved in tetrahydrofuran (100 ml), and butyllithium (1.6M hexane solution) (80 ml) was added dropwise to this solution at −5° C. with stirring. Thereafter, the mixture was stirred under ice-cooling for 1 hr, and a solution (50 ml) of methyl 7-methoxybenzo(b)furan-2-carboxylate (11.2 g) in tetrahydrofuran was added. The mixture was stirred at room temperature for 20 hr. A solution of sulfuric acid (28 g) dissolved in tetrahydrofuran (120 ml)-water (30 ml) was prepared, into which the reaction mixture was poured. The mixture was refluxed under heating for 2 hr. After cooling, the reaction mixture was poured into ice water and extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (2.1 g).

1. customThis was used in the next reaction without purification
2. stirringThereafter, the mixture was stirred under ice-
3. temperaturecooling for 1 hr
4. stirringThe mixture was stirred at room temperature for 20 hr
5. customwas prepared, into which the reaction mixture
6. additionwas poured
7. temperatureThe mixture was refluxed
8. temperatureunder heating for 2 hr
9. temperatureAfter cooling
10. extractionextracted with chloroform
11. dry with materialThe organic layer was dried over anhydrous sodium sulfate
12. concentrationconcentrated under reduced pressure
13. customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

ORD record

ord-c45388978c7f47fa954422fa8672308e

Source dataset

uspto-grants-2007_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07196199B2