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

HRID 897117

Reaction equation

HRID 897117 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 and then stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue was partitioned between ethyl acetate (100 ml) and water (100 ml). The organic layer was separated and the aqueous layer was extracted with further ethyl acetate (100 ml). The combined organic extracts were dried over anhydrous sodium sulphate and the solvent was 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 was partitioned between ethyl acetate (100 ml) and water (100 ml)
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with further ethyl acetate (100 ml)
  6. dry with materialThe combined organic extracts were dried over anhydrous sodium sulphate
  7. customthe solvent was 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-b3a281a78c634726adde3ab8efe671a2
Source dataset
uspto-grants-2005_07
Patent number
US06921753B2

Linked notes

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