1H-Isoindole-1,3(2H)-dione, 2-(2-bromoethyl)- → 2-[2-(4-isopropyl-1-piperidinyl)ethyl]-1H-isoindole-1,3(2H)-dione

HRID 10447

Reaction equation

HRID 10447 reaction equation
[CH:1]([CH:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1)([CH3:3])[CH3:2].Br[CH2:11][CH2:12][N:13]1[C:17](=[O:18])[C:16]2=[CH:19][CH:20]=[CH:21][CH:22]=[C:15]2[C:14]1=[O:23].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH:1]([CH:4]1[CH2:9][CH2:8][N:7]([CH2:11][CH2:12][N:13]2[C:14](=[O:23])[C:15]3[C:16](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17]2=[O:18])[CH2:6][CH2:5]1)([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 113251H-Isoindole-1,3(2H)-dione, 2-(2-bromoethyl)-HCID 11430Potassium CarbonateHCID 140569Piperidine, 4-(1-methylethyl)-

Product 1

HCID 219782572-[2-(4-isopropyl-1-piperidinyl)ethyl]-1H-isoindole-1,3(2H)-dioneYield 54.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 4-isopropylpiperidine (3.3 g, 20.2 mmol), N-(2-bromoethyl)phthalimide (5.4 g, 21.3 mmol), potassium carbonate (5.9 g, 45.4 mmol) and acetonitrile (100 ml) and was heated under reflux for 2.5 hours then stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue partitioned between ethyl acetate (100 ml) and water (100 ml). The organic layer was separated and the aqueous layer extracted with further ethyl acetate (100 ml). The combined organic extracts were dried (Na2SO4) and the solvent removed by evaporation under reduced pressure. The resulting oil was purified by column chromatography on silica gel eluting with a gradient system of dichloromethane changing to dichloromethane:diethyl ether (50:50, by volume) changing to diethyl ether to afford the title compound (3.3 g).

Workup

  1. temperatureunder reflux for 2.5 hours
  2. customThe solvent was removed under reduced pressure
  3. customthe residue partitioned between ethyl acetate (100 ml) and water (100 ml)
  4. customThe organic layer was separated
  5. extractionthe aqueous layer extracted with further ethyl acetate (100 ml)
  6. dry with materialThe combined organic extracts were dried (Na2SO4)
  7. customthe solvent removed by evaporation under reduced pressure
  8. customThe resulting oil was purified by column chromatography on silica gel eluting with a gradient system of dichloromethane changing to dichloromethane:diethyl ether (50:50, by volume)

Sources & evidence

ORD record
ord-7efd89374aa24ed08aa7d37e2d91e9b1
Source dataset
uspto-grants-2006_08
Patent number
US07094769B2

Linked notes

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