4-Bromoaniline → 2-(1-Azabicyclo[2.2.2]oct-3-yl)-N-(4-bromophenyl)acetamide Hydrochloride

HRID 722172Notes

Reaction equation

HRID 722172 reaction equation
[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[CH:3]([CH2:9][C:10]([OH:12])=O)[CH2:2]2.FC1C(O)=C(F)C(F)=C(F)C=1F.[ClH:25].CN(C)CCCN=C=NCC.[Br:37][C:38]1[CH:44]=[CH:43][C:41]([NH2:42])=[CH:40][CH:39]=1.C(=O)(O)[O-].[Na+]>ClCCl.C(OCC)(=O)C>[ClH:25].[N:1]12[CH2:6][CH2:5][CH:4]([CH2:7][CH2:8]1)[CH:3]([CH2:9][C:10]([NH:42][C:41]1[CH:43]=[CH:44][C:38]([Br:37])=[CH:39][CH:40]=1)=[O:12])[CH2:2]2

Participants

8

Reactant 5

HCID 78074-BromoanilineHCID 13041PentafluorophenolHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 103521012-(Quinuclidin-3-yl)acetic acid

Product 1

HCID 218834482-(1-Azabicyclo[2.2.2]oct-3-yl)-N-(4-bromophenyl)acetamide Hydrochloride

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

500 mg (2.43 mmol) of 1-azabicyclo[2.2.2]oct-3-ylacetic acid are dissolved in 10 ml of dichloromethane. At 0° C., 1.79 g (9.72 mmol) of pentafluorophenol and 699 mg (3.65 mmol) of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride are added. Stirring at room temperature for 14 h is followed by concentration in vacuo, dissolving of the residue in 8 ml of dimethylformamide, addition of 627 mg (3.65 mmol) of p-bromoaniline and stirring further at room temperature for 14 h. 10 ml of 10% strength sodium bicarbonate solution and 10 ml of ethyl acetate are slowly added. The resulting precipitate is filtered off with suction, and the filtrate is extracted three times with ethyl acetate. After drying over sodium sulfate, concentration results in a precipitate, which is filtered off. The solid is suspended in dioxane, mixed with 4M HCl in dioxane and stirred at room temperature for 30 minutes. Renewed filtration of the solid with suction results in 621 mg (71% of theory) of the title compound in the form of white crystals.

Workup

  1. concentrationis followed by concentration in vacuo
  2. dissolutiondissolving of the residue in 8 ml of dimethylformamide
  3. stirringstirring further at room temperature for 14 h
  4. filtrationThe resulting precipitate is filtered off with suction
  5. extractionthe filtrate is extracted three times with ethyl acetate
  6. dry with materialAfter drying over sodium sulfate, concentration
  7. customresults in a precipitate, which
  8. filtrationis filtered off
  9. additionmixed with 4M HCl in dioxane
  10. stirringstirred at room temperature for 30 minutes
  11. filtrationRenewed filtration of the solid with suction

Sources & evidence

ORD record
ord-9a471bd78631491cb30549a308dd815c
Source dataset
uspto-grants-2006_11
Patent number
US07138410B2

Reaction notes

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