tert-Butyl hydroperoxide → HCID 17862545, compound

1-Oxo-1,3-dihydroisobenzofuran-5-carbonitrile (1.56 g, 9.78 mmol) obtained from in Example 4-(4) was suspended in tetrahydrofuran (15 ml), and an aqueous solution of sodium hydroxide (1.008N; 9.70 ml, 9.78 mmol) was added thereto. The mixture was stirred at room temperature for 15 minutes and the solvent was distilled off under reduced pressure. The residue was dried using a vacuum pump to give an amorphous solid. The solid was dissolved in N,N-dimethylformamide (30 ml), and 4-methoxybenzyl chloride (1.53 g, 9.78 mmol) was added thereto, and then the mixture was stirred at 80° C. for 5 minutes. After the mixture was cooled to 0° C., a saturated aqueous solution of ammonium chloride was added thereto, and the product was extracted with ethyl acetate. The organic layer was washed with water and with a saturated aqueous solution of sodium chloride, and the solvent was distilled off under reduced pressure to give an oily residue. The residue was dissolved in dichloromethane (50 ml), and tetrazole (1.40 g, 20 mmol) and bis(allyloxy)(diisopropylamino)phosphine (Tetrahedron Lett., 30, 4219 (1989); 3.43 g, 14 mmol) were added thereto at 0° C., and then the resulting mixture was stirred at the same temperature for 5 minutes. The mixture was warmed to room temperature and stirred for 20 minutes, and then methanol (0.5 ml) was added thereto. The mixture was stirred for 10 minutes and cooled to 0° C., and tert-butyl hydroperoxide (80% di-tert-butyl peroxide solution; Merck; 2.7 g, 24 mmol) was added thereto, and then the reaction mixture was warmed to room temperature followed by stirring 20 minutes. A saturated aqueous solution of sodium hydrogen carbonate and an aqueous solution of sodium thiosulfate were added to the reaction mixture, and the resulting mixture was stirred for 10 minutes and partitioned between ethyl acetate and water. The organic layers were combined and the solvent was distilled off under reduced pressure to give a residue. The residue was subjected to chromatography on a silica gel (120 g) column (eluent; ethyl acetate:hexane=2:3) to afford a mixture of a solid and an oily material. The mixture was washed with a mixed solvent of ethyl acetate-hexane, and the washings were concentrated to give a residue. The residue was subjected to chromatography on a silica gel (50 g) column (eluent; ethyl acetate:hexane=2:3) to afford the title compound (1.18 g, 26% yield) as a colorless oil.

1. distillationthe solvent was distilled off under reduced pressure
2. customThe residue was dried
3. customto give an amorphous solid
4. stirringthe mixture was stirred at 80° C. for 5 minutes
5. temperatureAfter the mixture was cooled to 0° C.
6. extractionthe product was extracted with ethyl acetate
7. washThe organic layer was washed with water and with a saturated aqueous solution of sodium chloride
8. distillationthe solvent was distilled off under reduced pressure
9. customto give an oily residue
10. stirringat 0° C., and then the resulting mixture was stirred at the same temperature for 5 minutes
11. temperatureThe mixture was warmed to room temperature
12. stirringstirred for 20 minutes
13. stirringThe mixture was stirred for 10 minutes
14. temperaturecooled to 0° C.
15. temperaturethe reaction mixture was warmed to room temperature
16. stirringby stirring 20 minutes
17. stirringthe resulting mixture was stirred for 10 minutes
18. custompartitioned between ethyl acetate and water
19. distillationthe solvent was distilled off under reduced pressure
20. customto give a residue
21. customto afford
22. additiona mixture of a solid
23. washThe mixture was washed with a mixed solvent of ethyl acetate-hexane
24. concentrationthe washings were concentrated
25. customto give a residue

ORD record

ord-39134207c6244c5da92a428eea091da8

Source dataset

uspto-grants-2007_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07230023B2