1-[4-(1H-indol-3-yl)piperidino]ethan-1-one → HCID 14931742, compound

To a solution of 3-(1-acetyl-4-piperidyl)indole (48.2 g) in acetic acid (1 l) was added sodium cyanoborohydride (95 g) at 15° to 20° C. slowly over a period of 1.5 hours with stirring. The mixture was further stirred at ambient temperature for 3 hours, after which a further amount (10 g) of sodium cyanoborohydride was added. The mixture was stirred for 1 hour and the reaction mixture was diluted with water (500 ml), concentrated under reduced pressure, and allowed to stand overnight. To this reaction mixture was added 2N aqueous sodium hydroxide solution (1.5 l), and the mixture was extracted with ethyl acetate (1 l) 3 times. The extract was washed with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. The solvent was distilled off and the residue was dissolved in a mixture of tetrahydrofuran (200 ml) and 2N aqueous sodium hydroxide solution (300 ml). The solution was stirred at ambient temperature for 2 hours, after which it was concentrated under reduced pressure. The residue was extracted with ethyl acetate (600 ml) and the extract was washed with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. The solvent was distilled off and the residue was subjected to column chromatography on silica gel, elution being carried out with a mixture of chloroform and methanol (50:1 V/V) to give 3-(1-acetyl-4-piperidyl)indoline (41.1 g).

1. stirringThe mixture was further stirred at ambient temperature for 3 hours
2. stirringThe mixture was stirred for 1 hour
3. concentrationconcentrated under reduced pressure
4. additionTo this reaction mixture was added 2N aqueous sodium hydroxide solution (1.5 l)
5. extractionthe mixture was extracted with ethyl acetate (1 l) 3 times
6. washThe extract was washed with a saturated aqueous solution of sodium chloride
7. dry with materialdried over magnesium sulfate
8. distillationThe solvent was distilled off
9. dissolutionthe residue was dissolved in a mixture of tetrahydrofuran (200 ml) and 2N aqueous sodium hydroxide solution (300 ml)
10. stirringThe solution was stirred at ambient temperature for 2 hours
11. concentrationafter which it was concentrated under reduced pressure
12. extractionThe residue was extracted with ethyl acetate (600 ml)
13. washthe extract was washed with a saturated aqueous solution of sodium chloride
14. dry with materialdried over magnesium sulfate
15. distillationThe solvent was distilled off
16. washthe residue was subjected to column chromatography on silica gel, elution
17. additionbeing carried out with a mixture of chloroform and methanol (50:1 V/V)

ORD record

ord-76eb209cec7f44c88438c6bf88ed33c7

Source dataset

uspto-grants-1988_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04742057