Sodium Iodide → HCID 53742785, compound

HRID 2119385Notes

Reaction equation

HRID 2119385 reaction equation
C(=O)([O-])[O-].[K+].[K+].[CH3:7][C@H:8]1[NH:13][C@@H:12]([CH3:14])[CH2:11][N:10]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:9]1.Br[CH2:23][CH2:24][N:25]1[C:29](=[O:30])[C:28]2=[CH:31][CH:32]=[CH:33][CH:34]=[C:27]2[C:26]1=[O:35].[I-].[Na+]>C(#N)C>[NH3:10].[O:35]=[C:26]1[C:27]2[C:28](=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:29](=[O:30])[N:25]1[CH2:24][CH2:23][N:13]1[C@@H:8]([CH3:7])[CH2:9][N:10]([C:15]([O:17][C:18]([CH3:19])([CH3:21])[CH3:20])=[O:16])[CH2:11][C@H:12]1[CH3:14]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 113251H-Isoindole-1,3(2H)-dione, 2-(2-bromoethyl)-HCID 11430Potassium CarbonateHCID 10822535tert-butyl (3R,5S)-3,5-dimethylpiperazine-1-carboxylate

Product 2

HCID 222AmmoniaHCID 53742785HCID 53742785, compoundYield 40.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Potassium carbonate (1.79 g) was added to a solution of tertbutyl (cis)-3,5-dimethyl-1-piperazinecarboxylate (2.57 g) [see Preparation 5] in acetonitrile (10 ml). The reaction mixture was stirred at room temperature for 5 minutes, after which time N(2-bromoethyl) phthalimide (3.36 g) was added and the mixture was stirred for a further 4 hours. Sodium iodide (0.1 g) was added and the reaction mixture was heated to reflux for 18 hours. The mixture was then cooled and the solvent removed under reduced pressure. The residue was partitioned between ethyl acetate and water, the organic layer was separated, dried over magnesium sulphate and the solvent removed under reduced pressure. The crude product was purified by column chromatography on silica gel eluting with a solvent gradient of 4:1:0, changing to 0:95:5, by volume, hexane:ethyl acetate:0.88 aqueous ammonia solution, to afford tert-butyl (cis)-4-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3,5-dimethyl-1-piperazinecarboxylate (0.94 g) as an oil.

Workup

  1. stirringthe mixture was stirred for a further 4 hours
  2. temperaturethe reaction mixture was heated
  3. temperatureto reflux for 18 hours
  4. temperatureThe mixture was then cooled
  5. customthe solvent removed under reduced pressure
  6. customThe residue was partitioned between ethyl acetate and water
  7. customthe organic layer was separated
  8. dry with materialdried over magnesium sulphate
  9. customthe solvent removed under reduced pressure
  10. customThe crude product was purified by column chromatography on silica gel eluting with a solvent gradient of 4:1:0

Sources & evidence

ORD record
ord-4630047cdaa94655b4dda4d018ebf4fd
Source dataset
uspto-grants-2004_02
Patent number
US06686357B1

Reaction notes

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