Sodium ethoxide → 6-Iodo-2-oxindole

Temperature

20 °C

To a jacketed reactor, N,N-dimethylacetamide (DMAc) (120 mL) and sodium ethylate (NaOEt) powder (12.1 g) is charged at 20° C. Diethylmalonate (28.8 g) is added dropwise into the above mixture while keeping internal temperature at around 10° C. After finishing addition, warm up the mixture to 20° C., and continue to stir for another 10 minutes. Then, 2-chloro-5-iodonitrobenzene (17 g) is added in one portion, and heat the mixture to 78° C. and stir for usually at least 2.5 hours until process monitor shows almost complete conversion. The resulting mixture is cooled down to 20° C., and it is quenched by 2 N cold aq. HCl solution (180 mL). The bottom yellow oil was transferred to a jacket reactor with ethanol (92 mL) in it. Then, to the above solution the first portion of SnCl2.2H2O (30 g) powder is added, and the resulting mixture is heated to 70° C. and stirred for 1 hour. The second portion of SnCl2.2H2O (30 g) is added, the mixture is stirred usually at least 0.5 hour until process monitor shows almost complete conversion. Then, heat the resulting mixture to 80° C. and add 36% aq. HCl solution (60 mL) during 0.5 hour. The mixture is stirred for at least 2.5 hours until process monitor shows almost complete conversion. Then, to the mixture water (90 mL) is added and the resulting mixture is cooled down to 20° C. Collect the solid by filtration and wash the solid with water (250 mL) to afford the crude 6-iodo-2-oxindole. Then, it is purified by crystallization with acetic acid (HOAc) (110 mL), and followed by washing with 3 N aq. HCl solution (80 mL) to afford the 6-iodo-2-oxindole in 53% yield and 99% HPLC purity (Rt=7.45 min).

1. customat around 10° C
2. additionaddition
3. temperatureheat the mixture to 78° C.
4. stirringstir for usually at least 2.5 hours until process monitor
5. temperatureThe resulting mixture is cooled down to 20° C.
6. customit is quenched by 2 N cold aq. HCl solution (180 mL)
7. customThe bottom yellow oil was transferred to a jacket reactor with ethanol (92 mL) in it
8. additionThen, to the above solution the first portion of SnCl2.2H2O (30 g) powder is added
9. temperaturethe resulting mixture is heated to 70° C.
10. stirringstirred for 1 hour
11. additionThe second portion of SnCl2.2H2O (30 g) is added
12. stirringthe mixture is stirred usually at least 0.5 hour until process monitor
13. temperatureThen, heat the resulting mixture to 80° C.
14. additionadd 36% aq. HCl solution (60 mL) during 0.5 hour
15. stirringThe mixture is stirred for at least 2.5 hours until process monitor
16. additionThen, to the mixture water (90 mL) is added
17. temperaturethe resulting mixture is cooled down to 20° C
18. customCollect the solid
19. filtrationby filtration
20. washwash the solid with water (250 mL)
21. customto afford the crude 6-iodo-2-oxindole
22. customThen, it is purified by crystallization with acetic acid (HOAc) (110 mL)
23. washby washing with 3 N aq. HCl solution (80 mL)

ORD record

ord-83968f79b26a487cabd3a27d1342fb43

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08975418B2