Hydrochloric Acid → 8-bromo-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 501194Notes

Reaction equation

HRID 501194 reaction equation
Cl.[Br:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9]N)=[CH:5][CH:4]=1.Cl.[NH:12]1[CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]1.Cl>C(O)C>[Br:2][C:3]1[CH:8]=[CH:7][C:6]2[NH:9][C:15]3[CH2:16][CH2:17][NH:12][CH2:13][C:14]=3[C:5]=2[CH:4]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 121574-Bromophenylhydrazine hydrochlorideHCID 30848514-Piperidone hydrochloride

Product 1

HCID 47778528-bromo-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoleYield 101.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To a stirred solution of 4-bromophenylhydrazine hydrochloride (5.0 g, 22.36 mmol) in ethanol (100 mL), piperidin-4-one hydrochloride (1.316 g, 8.5984 mmol) was added and the mixture was heated to reflux. The reflux was maintained for 4 hours, then cooled to room temperature and dry hydrogen chloride gas was passed for 1 hour through the reaction mixture. The mixture was then again heated to reflux and maintained for 2 h. After completion of reaction, ethanol was distilled off under vacuum and the residue was dissolved in water. The aqueous layer was neutralized with 2N sodium hydroxide solution and was extracted in dichloromethane (2×100 mL). The pH of the aqueous layer was then adjusted to 12.0 with 2N sodium hydroxide solution and the product was extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate and concentrated under vacuum. The crude solid was washed with diethyl ether (50 mL) to obtain 8-bromo-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (2.2 g, 39.3%) with purity 98.82% by HPLC. 1HNMR (200 MHz, DMSO-d6) δ: 2.7 (t, 2H, CH2), 3.0 (t, 2H, CH2), 3.8 (d, 2H, CH2), 7.05 (d, 1H, Ar—H), 7.2 (d, 1H, Ar—H), 7.45 (s, 1H, Ar—H), 10.97 (bs, 1H, NH). m/e=251 (M++1).

Workup

  1. temperaturethe mixture was heated to reflux
  2. temperatureThe reflux was maintained for 4 hours
  3. temperatureThe mixture was then again heated
  4. temperatureto reflux
  5. temperaturemaintained for 2 h
  6. distillationwas distilled off under vacuum
  7. dissolutionthe residue was dissolved in water
  8. extractionwas extracted in dichloromethane (2×100 mL)
  9. extractionthe product was extracted with ethyl acetate
  10. dry with materialThe ethyl acetate layer was dried over anhydrous sodium sulfate
  11. concentrationconcentrated under vacuum
  12. washThe crude solid was washed with diethyl ether (50 mL)

Sources & evidence

ORD record
ord-b3fef86861744c3fac538ad56a3d9d54
Source dataset
uspto-grants-2010_08
Patent number
US07772245B2

Reaction notes

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