反应详情

温度

22.5 °C

Aluminium chloride (93.3 g, 700 mmol, 3.5 eq.) is suspended in 1,2-dichlorobenzene (320 mL). The suspension is maintained at 20-25° C. and 8-hydroxy-(1H)-quinolin-2-one (32.24 g, 200 mmol, 1.0 eq.) is added in 5 portions (40 minutes, IT max. 25° C.). Acetic anhydride (21.4 g, 210 mmol, 1.05 eq.) is slowly added (30 minutes, IT max. 20° C.) and the addition funnel is rinsed with a small amount of 1,2-dichlorobenzene. The suspension is stirred for 30 minutes at 20-25° C. HPLC control reveals complete conversion to 8-acetoxy-(1H)-quinolin-2-one. The mixture is heated to IT=80° C. while purging the head-space with a stream of nitrogen. HCl evolution is noticed upon reaching IT=40° C. The reaction mixture is stirred for 1 hour at IT=80° C. HPLC control reveals almost complete conversion to 5-acetyl-8-hydroxy-(1H)-quinolin-2-one (3.1% O-acetyl intermediate, 10.8% ortho-isomer). The reaction mixture is poured hot (80° C.) over water (800 mL). Water (100 mL) is added in the reaction vessel and brought to reflux temperature. After 15 minutes at reflux temperature, the suspension is added to the previous quench suspension. The mixture is maintained for 15 minutes at IT=80° C. and then hot filtered. The yellow product is rinsed with water (2×200 mL, 50° C.), rinsed with acetone (50 mL) and then dried overnight under vacuum at 70° C. Yield: 33.32 g (82.0%). Purity: 95-97%.

1. washthe addition funnel is rinsed with a small amount of 1,2-dichlorobenzene
2. temperatureThe mixture is heated to IT=80° C.
3. customwhile purging the head-space with a stream of nitrogen. HCl evolution
4. customIT=40° C
5. stirringThe reaction mixture is stirred for 1 hour at IT=80° C
6. additionThe reaction mixture is poured hot (80° C.) over water (800 mL)
7. additionWater (100 mL) is added in the reaction vessel
8. temperatureto reflux temperature
9. temperatureAfter 15 minutes at reflux temperature
10. additionthe suspension is added to the previous quench suspension
11. temperatureThe mixture is maintained for 15 minutes at IT=80° C.
12. washThe yellow product is rinsed with water (2×200 mL, 50° C.)
13. washrinsed with acetone (50 mL)
14. customdried overnight under vacuum at 70° C