2-Pyrrolidone → 1-(4-Iodobenzyl)pyrrolidin-2-one

HRID 230627Notes

Reaction equation

HRID 230627 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][C:2]1=[O:6].[H-].[Na+].[I:9][C:10]1[CH:17]=[CH:16][C:13]([CH2:14]Br)=[CH:12][CH:11]=1>CN(C)C=O>[I:9][C:10]1[CH:17]=[CH:16][C:13]([CH2:14][N:1]2[CH2:5][CH2:4][CH2:3][C:2]2=[O:6])=[CH:12][CH:11]=1

Participants

5

Reactant 3

HCID 120252-PyrrolidoneHCID 24758Sodium hydrideHCID 9542584-Iodobenzyl bromide

Product 1

HCID 509928621-(4-Iodobenzyl)pyrrolidin-2-oneYield 99%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-pyrrolidinone (850 mg, 10 mmol) in dimethylformamide (40 ml) was cooled in an ice/methanol bath with stirring under an atmosphere of argon. Then a solid suspension of sodium hydride (60% in mineral oil, 440 mg, 11 mmol) was added portionwise over 10 minutes. The reaction mix was allowed to stir with cooling for 30 minutes, then 4-iodobenzyl bromide (2.97 g, 10 mmol) was added portionwise over 10 minutes. The whole mix was allowed to warm slowly up to room temperature then stirred for a further 2 hours. The reaction mixture was partitioned between ethyl acetate (100 ml), and water (200 ml), the organic layer was removed and reduced to minimum volume under reduced pressure. The residue was purified by column chromatography on a 20 g pre-packed silica column eluting from 0-100% ethyl acetate in petroleum ether to give the title compound as a yellow solid (2.97 g, 99%).

Workup

  1. additionwas added portionwise over 10 minutes
  2. additionThe reaction mix
  3. stirringto stir
  4. temperaturewith cooling for 30 minutes
  5. additionThe whole mix
  6. stirringthen stirred for a further 2 hours
  7. customThe reaction mixture was partitioned between ethyl acetate (100 ml), and water (200 ml)
  8. customthe organic layer was removed
  9. customThe residue was purified by column chromatography on a 20 g pre-packed silica column
  10. washeluting from 0-100% ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-ae1edad3fd224381829d59ec440bc331
Source dataset
uspto-grants-2009_07
Patent number
US07566735B2

Reaction notes

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