Hydrochloric Acid → HCID 70036578, compound

Temperature

0 °C

To a suspended solution of 4-(3-indolyl)piperidine (200 mg, 1.0 mmol) in dichloromethane (15 mL) was added pyridine (5 mL), and the resulting mixture was cooled to 0° C. Subsequently, 3-chloropropionyl chloride (0.25 mL, 2.6 mmol) was then added dropwise to the mixture, and the resulting mixture was stirred at 0° C. for 2 hours. After the reaction mixture was poured into hydrochloric acid and then extracted with ethyl acetate, the ethyl acetate layer was washed with 1 N hydrochloric acid and a saturated aqueous sodium chloride and was dried over anhydrous sodium sulfate. After sodium sulfate was filtered off, the filtrate was concentrated to afford a crude product (100 mg). After identifying the structure of the crude product by 1H NMR and IR, piperidine (350 mg, 4.0 mmol) was added to a solution of the crude product in acetonitrile (10 mL), and the mixture was stirred at 80° C. for 3 hours. After concentrating the reaction mixture, water (10 mL) was added thereto, and the resulting mixture was extracted with chloroform. After drying over anhydrous sodium sulfate, the chloroform layer was concentrated, and the resulting crude product was purified by column chromatography on a silica gel (silica gel NH-DM 1020 produced by Fuji Silysia Chemical Ltd., eluent; hexane:ethyl acetate=1:2) to afford a free form (97 mg, yield: 29%) of the title compound as a colorless amorphous solid. After adding hydrochloric acid/methanol to a solution of the free form (67 mg) in methanol, the mixture was concentrated and was then reprecipitated from ethanol/ether to afford the title compound (50 mg) as a pale yellow amorphous solid.

1. extractionextracted with ethyl acetate
2. washthe ethyl acetate layer was washed with 1 N hydrochloric acid
3. dry with materiala saturated aqueous sodium chloride and was dried over anhydrous sodium sulfate
4. filtrationAfter sodium sulfate was filtered off
5. concentrationthe filtrate was concentrated
6. customto afford a crude product (100 mg)
7. stirringthe mixture was stirred at 80° C. for 3 hours
8. concentrationAfter concentrating the reaction mixture, water (10 mL)
9. additionwas added
10. extractionthe resulting mixture was extracted with chloroform
11. dry with materialAfter drying over anhydrous sodium sulfate
12. concentrationthe chloroform layer was concentrated
13. customthe resulting crude product was purified by column chromatography on a silica gel (silica gel NH-DM 1020 produced by Fuji Silysia Chemical Ltd., eluent; hexane:ethyl acetate=1:2)

ORD record

ord-24e0c067b34e4a7fbeec70f3de610db4

Source dataset

uspto-grants-2003_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06642228B1