Acetic Acid → 5-Chloro-1-(4-fluorophenyl)-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole

HRID 1250032Notes

Reaction equation

HRID 1250032 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)[CH:6]=[CH:5]2.[C:18](O)(=O)[CH3:19].Cl>CC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)[CH:6]=[C:5]2[C:4]1[CH2:5][CH2:6][NH:7][CH2:18][CH:19]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 102361885-Chloro-1-(4-fluorophenyl)-1H-indole

Product 1

HCID 98838385-Chloro-1-(4-fluorophenyl)-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
60 °C

Procedure

5-chloro-1-(4-fluorophenyl)indole (6.70 kg) and 4-piperidone-mono-hydrate,hydrochloride (8.38 kg) were transferred to a 200 L reactor under N2 cover. Acetic acid (67 L) was added and the reaction mixture was heated to 60° C. Concentrated HCl (37%, 33.5 L) was added during ½ hour and then the mixture was heated to the reflux temperature (85° C.) and refluxed for 1 hour (final temperature 95° C.). After cooling to 30° C., 33.5 L acetone was added followed by further cooling to 25° C. Filtration, wash (acetone 20 L) and drying in vacuum at 60° C. gave the title product as a white powder, yield 8.94 kg.

Workup

  1. temperaturethe mixture was heated to the reflux temperature (85° C.)
  2. temperaturerefluxed for 1 hour (final temperature 95° C.)
  3. temperatureAfter cooling to 30° C.
  4. temperatureby further cooling to 25° C
  5. filtrationFiltration
  6. washwash (acetone 20 L)
  7. customdrying in vacuum at 60° C.

Sources & evidence

ORD record
ord-de443f8748cc4b6b8bd50426c69e2f7b
Source dataset
uspto-grants-2002_01
Patent number
US06335463B1

Reaction notes

Loading…