反应详情

Methyl 3-oxobutanoate (29.4 g) was dissolved in methanol (30 ml), then a 40%-methylamine-methanol solution (32 ml) was added dropwise at room temperature, and the mixture was stirred for 1 hour. After the completion of the reaction, the reaction solution as such was concentrated, and then dried using a vacuum pump to obtain methyl 3-(methylamino)-2-butenoate (31.8 g, yield 97%). Subsequently, methyl 3-(methylamino)-2-butenoate (1.0 g) was dissolved in tetrahydrofuran (15 ml) and pyridine (0.63 ml) was added dropwise at room temperature. Under ice cooling, m-toluyl chloride (1.22 ml) was added dropwise and the mixture was stirred at room temperature for 1 hour. After the completion of the reaction, distilled water was added, and the reaction product was extracted by liquid separation using ether and then washed with a saturated saline solution. The product was dried over sodium sulfate to concentrate and the residue was dried using a vacuum pump. Subsequently, the residue was dissolved in an acetic acid (15 ml). Then, hydroxylamine hydrochloride (0.54 g) was added at room temperature, and the product was heated under reflux for 30 minutes. After the completion of the reaction, saturated aqueous solution of sodium hydrogencarbonate was added to neutralize the reaction system, and the product was extracted by liquid separation using ether. The resultant organic layer was washed with saturated aqueous solution of sodium chloride and dried over sodium sulfate to concentrate. The residue was purified by silica gel column chromatography using a hexane-acetone elution system to obtain methyl 3-methyl-5-(3-methylphenyl)-4-isoxazole carboxylate (183 mg, yield 10.2%).

1. customAfter the completion of the reaction
2. distillationdistilled water
3. additionwas added
4. extractionthe reaction product was extracted by liquid separation
5. washwashed with a saturated saline solution
6. dry with materialThe product was dried over sodium sulfate
7. concentrationto concentrate
8. customthe residue was dried
9. dissolutionSubsequently, the residue was dissolved in an acetic acid (15 ml)
10. additionThen, hydroxylamine hydrochloride (0.54 g) was added at room temperature
11. temperaturethe product was heated
12. temperatureunder reflux for 30 minutes
13. customAfter the completion of the reaction, saturated aqueous solution of sodium hydrogencarbonate
14. additionwas added
15. extractionthe product was extracted by liquid separation
16. washThe resultant organic layer was washed with saturated aqueous solution of sodium chloride
17. dry with materialdried over sodium sulfate
18. concentrationto concentrate
19. customThe residue was purified by silica gel column chromatography
20. washa hexane-acetone elution system