Water → 8-Chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-one

HRID 2299258Notes

Reaction equation

HRID 2299258 reaction equation
P(Cl)(Cl)(Cl)=O.C1(N[C:13]([C:15]2[C:20]([CH2:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=3)=[CH:19][CH:18]=[CH:17][N:16]=2)=[O:14])C=CC=CC=1.O>ClC1C=CC=CC=1>[Cl:29][C:25]1[CH:26]=[CH:27][C:28]2[C:13](=[O:14])[C:15]3=[N:16][CH:17]=[CH:18][CH:19]=[C:20]3[CH2:21][CH2:22][C:23]=2[CH:24]=1

Participants

5

Reactant 3

HCID 962WaterHCID 24813Phosphorus oxychlorideHCID 9862612n-Phenyl-3-[2-(3chlorophenyl)ethyl]-2-pyridine carboxamide

Product 1

HCID 98162608-Chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-one

Reagents, catalysts & solvents 1

HCID 7964ChlorobenzeneSolvent2×

Procedure

A mixture of trifluroromethanesulfonic acid (63.2 ml; 0.71 mol) and phosphorus oxychloride (66.4 ml; 0.71 mol) in chlorobenzene (400 ml) was stirred for ½hour at room temperature. A solution of N-phenyl-3-[2-(3-chlorophenyl)ethyl]-2-pyridine carboxamide 4 (120 g; 0.36 mol) in chlorobenzene (240 ml) was added. The mixture was heated at 110° C. for 18 hours followed by cooling to 50° C. Water (400 ml) was added and the biphasic mixture heated to 80° C. for ½ hour. The mixture was cooled to room temperature, stirred vigorously for 10 minutes, then allowed to stand for 10 minutes. The product was removed by filtration and partitioned between water (300 ml) and toluene (500 ml). The pH of the aqueous phase was adjusted to 10 with 10M NaOH solution. 100 ml of the organic phase was removed by distillation under reduced pressure. Charcoal (5.5 g) was added and the mixture filtered through a pad of celite. The solution was concentrated under vacuum to 300 ml and 150 ml of hexane was added. The mixture was cooled to 0-10° C. for 1 hour with stirring prior to filtration. The product was washed with 100 ml of chilled toluene and then air-dried for several hours. Yield 44.1 g (50.8%)

Workup

  1. temperatureThe mixture was heated at 110° C. for 18 hours
  2. temperatureby cooling to 50° C
  3. temperaturethe biphasic mixture heated to 80° C. for ½ hour
  4. temperatureThe mixture was cooled to room temperature
  5. stirringstirred vigorously for 10 minutes
  6. customThe product was removed by filtration
  7. custompartitioned between water (300 ml) and toluene (500 ml)
  8. custom100 ml of the organic phase was removed by distillation under reduced pressure
  9. additionCharcoal (5.5 g) was added
  10. filtrationthe mixture filtered through a pad of celite
  11. concentrationThe solution was concentrated under vacuum to 300 ml and 150 ml of hexane
  12. additionwas added
  13. temperatureThe mixture was cooled to 0-10° C. for 1 hour
  14. stirringwith stirring
  15. filtrationto filtration
  16. washThe product was washed with 100 ml of chilled toluene
  17. customair-dried for several hours

Sources & evidence

ORD record
ord-6f0d946857634e1bbd8e5ca1d2906c9e
Source dataset
uspto-grants-2002_12
Patent number
US06495689B2

Reaction notes

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