反应详情

温度

-65 °C

Ethyl 5-(2-chloroacetylamino)-4-(2-chlorobenzoyl)thiophene-2-carboxylate (325 g) and sodium iodide (151.3 g) were added to tetrahydrofuran (3500 ml), and the mixture was refluxed under heating for 1.5 hours. The mixture was cooled to -65° C., and ammonia (164 ml) was added. The reaction temperature was raised slowly to room temperature. The solvent was evaporated, and chloroform and water were added. The organic layer was taken out, washed with water and dried over sodium sulfate. The solvent was evaporated. Toluene (7 l) and silica gel (1365 g) were added thereto, and the mixture was refluxed under heating for 1.5 hours. The silica gel was collected by filtration, and a mixed solvent of chloroform-methanol (10:1) was added to elute the obtained product. The solvent was evaporated, and ethyl acetate was added. The resulting crystals were collected by filtration and washed with ethyl acetate to give 70.0 g of ethyl (5-(2-chlorophenyl)-1,2-dihydro-3H-thieno[2,3-e] [1,4]diazepin-2-on-7-yl)-carboxylate.

1. temperaturethe mixture was refluxed
2. temperatureunder heating for 1.5 hours
3. temperatureThe reaction temperature was raised slowly to room temperature
4. customThe solvent was evaporated
5. additionchloroform and water were added
6. washwashed with water
7. dry with materialdried over sodium sulfate
8. customThe solvent was evaporated
9. additionToluene (7 l) and silica gel (1365 g) were added
10. temperaturethe mixture was refluxed
11. temperatureunder heating for 1.5 hours
12. filtrationThe silica gel was collected by filtration
13. additiona mixed solvent of chloroform-methanol (10:1) was added
14. washto elute the obtained product
15. customThe solvent was evaporated
16. additionethyl acetate was added
17. filtrationThe resulting crystals were collected by filtration
18. washwashed with ethyl acetate