1H-Isoindole-1,3(2H)-dione, 2-(2-bromoethyl)- → Ammonia

HRID 1363014Notes

Reaction equation

HRID 1363014 reaction equation
[CH2:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([O:15][CH:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)[CH:14]=1)[N:11]=[CH:10][CH:9]=[CH:8]2)[CH2:2][CH2:3][CH3:4].Br[CH2:23][CH2:24][N:25]1[C:33](=[O:34])[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]1=[O:35].C(=O)([O-])[O-].[K+].[K+]>CC(=O)CC>[NH3:11].[CH2:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([O:15][CH:16]3[CH2:17][CH2:18][N:19]([CH2:23][CH2:24][N:25]4[C:26](=[O:35])[C:27]5[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=5)[C:33]4=[O:34])[CH2:20][CH2:21]3)[CH:14]=1)[N:11]=[CH:10][CH:9]=[CH:8]2)[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 3

HCID 113251H-Isoindole-1,3(2H)-dione, 2-(2-bromoethyl)-3×HCID 11430Potassium CarbonateHCID 579260486-Butyl-8-(4-piperidinyloxy)quinoline2×

Product 2

HCID 222AmmoniaHCID 669219102-(2-{4-[(6-Butyl-8-quinolinyl)oxy]-1-piperidinyl}ethyl)-1H-isoindole-1,3(2H)-dione

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Procedure

6-Butyl-8-(4-piperidinyloxy)quinoline (for example, as prepared for Intermediate 4) (2.44 g, 8.59 mmol) was stirred with 2-(2-bromoethyl)-1H-isoindole-1,3(2H)-dione (commercially available, for example, from Acros and/or Aldrich) (2.40 g, 9.4 mmol) and potassium carbonate (5.9 g, 43 mmol) in 2-butanone (75 ml) under nitrogen at 80° C. for 3 days. Further 2-(2-bromoethyl)-1H-isoindole-1,3(2H)-dione (2.4 g, 9.4 mmol) was added and the heating and stirring were continued for a further 24 h. More 2-(2-bromoethyl)-1H-isoindole-1,3(2H)-dione (1.2 g, 4.7 mmol) was added and the heating and stirring were continued for a further 24 h. The mixture was cooled and partitioned between water and DCM. The aqueous layer was extracted with more DCM (×2) and the combined organic layers were washed with water, dried (MgSO4) and evaporated to an oil. This oil was re-dissolved in DCM and loaded onto a column of silica gel (250 g) that had been preconditioned with DCM. The column was eluted with DCM, then DCM-ethanol-0.88 s.g. aqueous ammonia solution (200:8:1) to give the title compound (2.76 g, 6.03 mmol). LCMS RT=2.91 min, ES+ve m/z 458 [M+H]+.

Workup

  1. stirringthe heating and stirring
  2. waitwere continued for a further 24 h
  3. temperatureThe mixture was cooled
  4. custompartitioned between water and DCM
  5. extractionThe aqueous layer was extracted with more DCM (×2)
  6. washthe combined organic layers were washed with water
  7. dry with materialdried (MgSO4)
  8. customevaporated to an oil
  9. dissolutionThis oil was re-dissolved in DCM
  10. washThe column was eluted with DCM
  11. customDCM-ethanol-0.88 s

Sources & evidence

ORD record
ord-d8d63738b4004dee9c15a10c940f0fa9
Source dataset
uspto-grants-2011_02
Patent number
US07884114B2

Reaction notes

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