反应详情

温度

0 °C

4-Amino-2-chloro-6-fluorobenzonitrile (293 mmol, 50 g) was dissolved in ACN (1550 ml) and water (460 ml). Sulphuric acid (879 mmol, 46.9 ml) was added carefully. The reaction mixture was cooled to 0° C. Sodium nitrite (322 mmol, 22.25 g) dissolved in water (150 ml) was slowly added keeping the reaction temperature below 10° C. Thereafter potassium iodide (586 mmol, 97 g) dissolved in 150 ml of water was added slowly while keeping the reaction temperature below 10° C. The reaction mixture was allowed to warm up to RT and stirred overnight at RT. The phases were separated and the organic phase was evaporated. Ethyl acetate was added into the evaporation residue and washed three times with 10% aqueous NaHSO3. The organic phase was evaporated and the residue was dissolved in DCM. 5 g of active carbon was added and stirred for 2 h. The mixture was filtered through a layer of Celite and washed with DCM. The DCM-phase was evaporated and heptanes were added into the residue. The mixture was heated to 60° C. and stirred for 2 h. The oil and heptanes layers were separated by decantation. The heptanes phase was evaporated and 39.6 g of the title compound was obtained. 1H-NMR (400 MHz, DMSO-d6): δ 8.06-8.10 (m, 1H), 8.10-8.11 (m, 1H).

1. additionwas slowly added
2. customthe reaction temperature below 10° C
3. additionwas added slowly
4. customthe reaction temperature below 10° C
5. temperatureto warm up to RT
6. customThe phases were separated
7. customthe organic phase was evaporated
8. additionEthyl acetate was added into the evaporation residue
9. washwashed three times with 10% aqueous NaHSO3
10. customThe organic phase was evaporated
11. dissolutionthe residue was dissolved in DCM
12. addition5 g of active carbon was added
13. stirringstirred for 2 h
14. filtrationThe mixture was filtered through a layer of Celite
15. washwashed with DCM
16. customThe DCM-phase was evaporated
17. additionheptanes were added into the residue
18. temperatureThe mixture was heated to 60° C.
19. stirringstirred for 2 h
20. customThe oil and heptanes layers were separated by decantation
21. customThe heptanes phase was evaporated