Pyridine → 5-Chloro-2-(4-piperidinyl)-1H-indole

Temperature

60 °C

A mixture of 0.60 gm (3.4 mMol) 4-chlorophenylhydrazine hydrochloride and 0.54 mL (6.7 mMol) pyridine in 20 mL ethanol were stirred at 60° C. for 15 minutes. To this mixture was then added 4-acetylpiperidine hydrochloride and the reaction mixture was stirred for 2 hours at 70° C. The reaction mixture was concentrated under reduced pressure and the residue was treated with polyphosphoric acid. This mixture was heated at 90°-100° C. for 48 hours. The reaction mixture was quenched with a slurry of ice in 5N sodium hydroxide. The aqueous mixture was extracted well with ethyl acetate. The organic phases were combined, washed with saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, eluting with a dichloromethane gradient containing 4-20% methanol. Fractions containing product were combined and concentrated under reduced pressure to provide 0.26 gm (36%) of the title compound as a tan solid.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. additionthe residue was treated with polyphosphoric acid
3. temperatureThis mixture was heated at 90°-100° C. for 48 hours
4. customThe reaction mixture was quenched with a slurry of ice in 5N sodium hydroxide
5. extractionThe aqueous mixture was extracted well with ethyl acetate
6. washwashed with saturated aqueous sodium chloride
7. dry with materialdried over sodium sulfate
8. concentrationconcentrated under reduced pressure
9. washeluting with a dichloromethane gradient
10. additioncontaining 4-20% methanol
11. additionFractions containing product
12. concentrationconcentrated under reduced pressure

ORD record

ord-0aab5862bcd54558a95f8702e607f584

Source dataset

uspto-grants-1998_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05846982