Isatin → Indole

Temperature

10 °C

The corresponding isatin 1a-1d (10 mmol) was dissolved in a mixture of ethanol/pyridine/acetic acid (50 ml, 15:5:2), ethyl potassium malonate (1.87 g, 11 mmol) was added and the mixture was heated under reflux in accordance with the times stated in the table. The course of the reaction was monitored by means of TLC (eluent: ethyl acetate/hexane 1:1). For working up, the solvent mixture was distilled off in vacuo. The residue was taken up in ethyl acetate (50 ml) and the mixture was extracted by shaking with water (50 ml). After separation of the phases, the aqueous phase was extracted twice with ethyl acetate (30 ml each time). The combined organic phases were washed with 2N HCl (50 ml), dried over Na2SO4 and concentrated to 20 ml in vacuo. Hexane was added to the solution until crystallization of the corresponding 3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)acetic acid ethyl ester (2a-2d) started. To bring the crystallization to completion, the mixture was cooled to 10° C. for 12 h. The solid was filtered off with suction and dried in vacuo.

1. additionwas added
2. temperaturethe mixture was heated
3. temperatureunder reflux in accordance with the times
4. distillationthe solvent mixture was distilled off in vacuo
5. extractionthe mixture was extracted
6. customAfter separation of the phases
7. extractionthe aqueous phase was extracted twice with ethyl acetate (30 ml each time)
8. washThe combined organic phases were washed with 2N HCl (50 ml)
9. dry with materialdried over Na2SO4
10. concentrationconcentrated to 20 ml in vacuo
11. additionHexane was added to the solution until crystallization of the corresponding 3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)acetic acid ethyl ester (2a-2d)
12. customthe crystallization to completion
13. filtrationThe solid was filtered off with suction
14. customdried in vacuo

ORD record

ord-4df55a2e0afb4b66967b926552009b62

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08138187B2