Acetic Anhydride → Methyl 3-cyano-1H-indole-5-carboxylate

A mixture of 3-formylindole-5-carboxylic acid (3.47 g), hydroxylamine hydrochloride (1.97 g) and sodium acetate (2.41 g) in acetic acid (30 ml) was stirred for 12 hours, then acetic anhydride (15 ml) was added to the mixture and allowed to react under reflux for 5 hours. After cooling, the reaction mixture was filtered and the filtrate was evaporated under reduced pressure. Methanol was added to the residue and the mixture was reevaporated under reduced pressure. Thionyl chloride (8 ml) and small amounts of N,N-dimethylformamide was added to the residue obtained above in dichloromethane (20 ml). After being stirred for 2 hours at room temperature, the reaction mixture was evaporated under reduced pressure, and the residue was treated with methanol and concentrated under reduced pressure. The residue was partitioned between aqueous sodium hydrogen carbonate solution and ethyl acetate. The ethyl acetate layer was washed with brine, dried over magnesium sulfate and evaporated under reduced pressure. The resulting residue was subjected to column chromatography on silica gel and eluted with a mixture of ethyl acetate and chloroform. The fractions containing the objective compounds were combined and concentrated under reduced pressure to give methyl 3-cyanoindole-5-carboxylate (2.87 g).

1. customto react
2. temperatureunder reflux for 5 hours
3. temperatureAfter cooling
4. filtrationthe reaction mixture was filtered
5. customthe filtrate was evaporated under reduced pressure
6. additionMethanol was added to the residue
7. customthe mixture was reevaporated under reduced pressure
8. additionThionyl chloride (8 ml) and small amounts of N,N-dimethylformamide was added to the residue
9. customobtained above in dichloromethane (20 ml)
10. stirringAfter being stirred for 2 hours at room temperature
11. customthe reaction mixture was evaporated under reduced pressure
12. additionthe residue was treated with methanol
13. concentrationconcentrated under reduced pressure
14. customThe residue was partitioned between aqueous sodium hydrogen carbonate solution and ethyl acetate
15. washThe ethyl acetate layer was washed with brine
16. dry with materialdried over magnesium sulfate
17. customevaporated under reduced pressure
18. washeluted with a mixture of ethyl acetate and chloroform
19. additionThe fractions containing the objective compounds
20. concentrationconcentrated under reduced pressure

ORD record

ord-8c9f5d44853449dea949c5b60ce5e72e

Source dataset

uspto-grants-1999_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05994378