反应详情

温度

-10 °C

The 1-methyl-5-phenyl-1,3-dihydro-azepin-2-one (183 g, 918.4 mmol) is combined with tetrahydrofuran (1500 mL) and the solution cooled to −25° C. to −30° C. Isoamyl nitrite (148.1 mL, 1.102 mol) is added followed by potassium tertiary-butoxide (108.2 g, 964.4 mmol) providing an exotherm to about −5° C. The solution is re-cooled to −10° C., then allowed to slowly warm to room temperature. The reaction contents are allowed to stir overnight. The reaction contents are diluted with 3N aqueous HCl (300 mL) providing a pH of about 2. It is then diluted with methyl tertiary-butyl ether (4 L) and washed the contents with 0.5-1.0 N HCl (2×600 mL) and saturated aqueous sodium chloride. The dark organic layer is dried over MgSO4, filtered, and concentrated to provide a residue wet with tetrahydrofuran. The residue is diluted with cyclohexane (300 mL) and concentrated to provide about 275 g of a crude residue that is slurried in methyl tertiary-butyl ether (450 mL) and cyclohexane (1000 mL). Heat the slurry to about 40° C., cool to room temperature, filter, and rinse with cyclohexane. Vacuum dry at 40° C. to provide the title compound (169 g, 81%) as a brown powder.

1. temperaturethe solution cooled to −25° C. to −30° C
2. customproviding an exotherm to about −5° C
3. temperatureto slowly warm to room temperature
4. customThe reaction contents
5. customThe reaction contents
6. customproviding a pH of about 2
7. washwashed the contents with 0.5-1.0 N HCl (2×600 mL) and saturated aqueous sodium chloride
8. dry with materialThe dark organic layer is dried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated
11. customto provide a residue wet with tetrahydrofuran
12. concentrationconcentrated
13. customto provide about 275 g of a crude residue that
14. temperatureHeat the slurry to about 40° C.
15. temperaturecool to room temperature
16. filtrationfilter
17. washrinse with cyclohexane
18. customVacuum dry at 40° C.