Acetate → Ethyl 1,2-benzoxazole-3-carboxylate

Temperature

50 °C

Ethyl 2-nitrophenyl)acetate (12.3 g, 58.6 mmol) and isoamyl nitrate (8.92 g, 76.1 mmol) were dissolved in ethanol (100 ml). Sodium methoxide (19.9 ml, 58.6 mmol, a 20% solution in ethanol) was added, followed by stirring at 50° C. for 1.5 hours. The reaction mixture was cooled to room temperature and neutralized with 1M HCl (30 ml), followed by extraction with ether. The extract was dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove the solvent. The residue was crystallized by the addition of chloroform/n-hexane and the crystals were dried under reduced pressure for 18 hours. The crystals thus obtained were dissolved in 1,2-dimethoxyethane (100 ml) and to the resulting solution, a solution of sodium hydride (2.81 g, 70.3 mmol) in 1,2-dimethoxyethane (100 ml) was added in portions. The reaction mixture was stirred at 150° C. for 8 hours. Under cooling, the reaction mixture was poured to a saturated aqueous solution of sodium bicarbonate, followed by extraction with ether. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography (middle pressure chromatography system Yamazen, n-hexane/ethyl acetate 9:1, 20 ml/min, φ 80×300) to give ethyl benzo(d)isoxazole-3-carboxylate (5.75 g, 51%) as a brown solid.

1. extractionfollowed by extraction with ether
2. dry with materialThe extract was dried over anhydrous magnesium sulfate
3. distillationdistilled under reduced pressure
4. customto remove the solvent
5. customThe residue was crystallized by the addition of chloroform/n-hexane
6. customthe crystals were dried under reduced pressure for 18 hours
7. customThe crystals thus obtained
8. stirringThe reaction mixture was stirred at 150° C. for 8 hours
9. temperatureUnder cooling
10. extractionfollowed by extraction with ether
11. washThe extract was washed with saturated brine
12. dry with materialdried over anhydrous magnesium sulfate
13. distillationdistilled under reduced pressure
14. customto remove the solvent
15. customThe residue was purified by silica gel column chromatography (middle pressure chromatography system Yamazen, n-hexane/ethyl acetate 9:1, 20 ml/min, φ 80×300)

ORD record

ord-e61d3963aaa74175b1fbc3d3ff17b960

Source dataset

uspto-grants-2007_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07157487B2