反应详情

温度

22.5 °C

8-Hydroxy-(1H)-quinolin-2-one (32.24 g, 200 mmol, 1.0 eq) is suspended in 1,2-dichloro benzene (300 mL). The suspension is maintained at 20-25° C. and aluminium chloride (93.3 g, 700 mmol, 3.5 eq.) is added in portions (30 minutes, IT max. 25 IC). 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 IC 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 (1.8% O-acetyl intermediate, 7.2% ortho-isomer). The reaction mixture is heated to IT=90° C. and poured hot (90 ° C.) over water (645 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 is hot filtered. The yellow product is rinsed with water (2×200 mL, 50° C.). The crude product (70.1 g) is suspended in acetic acid (495 mL) and the suspension is heated to reflux temperature for 30 minutes. The suspension is cooled down to IT=20° C. and then filtered. The product is washed with acetic acid/water 1/1 (60 mL) and washed with water (5×100 mL) before being dried at 70° C. under vacuum to yield the title compound in 75% yield (31.48 g) and with 99.9% purity.

1. washthe addition funnel is rinsed with a small amount of 1,2-dichlorobenzene
2. temperatureThe mixture is heated to IT=80 IC
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. temperatureThe reaction mixture is heated to IT=90° C.
7. additionpoured hot (90 ° C.) over water (645 mL)
8. additionWater (100 mL) is added in the reaction vessel
9. temperatureto reflux temperature
10. temperatureAfter 15 minutes at reflux temperature
11. additionthe suspension is added to the previous quench suspension
12. temperatureThe mixture is maintained for 15 minutes at IT=80° C.
13. washThe yellow product is rinsed with water (2×200 mL, 50° C.)
14. temperaturethe suspension is heated
15. temperatureto reflux temperature for 30 minutes
16. temperatureThe suspension is cooled down to IT=20° C.
17. filtrationfiltered
18. washThe product is washed with acetic acid/water 1/1 (60 mL)
19. washwashed with water (5×100 mL)
20. custombefore being dried at 70° C. under vacuum