Sodium Iodide → 1,4-dibutyl-1,3-dihydro-3-[(6-bromo-3-pyridinyl)methyl]-2H-imidazol-2-one

HRID 343585Notes

Reaction equation

HRID 343585 reaction equation
CC(C)([O-])C.[K+].[CH2:7]([N:11]1[CH:15]=[C:14]([CH2:16][CH2:17][CH2:18][CH3:19])[NH:13][C:12]1=[O:20])[CH2:8][CH2:9][CH3:10].[Br:21][C:22]1[CH:27]=[CH:26][C:25]([CH2:28]Br)=[CH:24][N:23]=1.[I-].[Na+]>C1COCC1.CN(C=O)C>[CH2:7]([N:11]1[CH:15]=[C:14]([CH2:16][CH2:17][CH2:18][CH3:19])[N:13]([CH2:28][C:25]2[CH:24]=[N:23][C:22]([Br:21])=[CH:27][CH:26]=2)[C:12]1=[O:20])[CH2:8][CH2:9][CH3:10]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 64246602-Bromo-5-bromomethylpyridineHCID 154057281,4-Dibutylimidazol-2-oneHCID 23665647Potassium tert-butoxide

Product 1

HCID 154057291,4-dibutyl-1,3-dihydro-3-[(6-bromo-3-pyridinyl)methyl]-2H-imidazol-2-oneYield 73%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Under nitrogen, 138 mL (138 mmol) of 1.0M potassium t-butoxide in THF was added to a stirred solution of 24.5 g (125 mmol) of 1,4-dibutylimidazol-2-one from step 2A in 370 mL of DMF at -30° C. at such a rate to maintain the solution temperature below -20° C. After 10 min, 50 g [138 mmol (69% purity)] of 2-bromo-5-bromomethylpyridine from step 4 and 2.7 g (18.1 mmol) of sodium iodide were added. The reaction was stirred at 0° C. for 2 h and then allowed to slowly warm to ambient temperature overnight. The reaction was partitioned between ethyl acetate and water; the organic layer was washed twice with brine and the combined aqueous phases were back-extracted with ethyl acetate. The ethyl acetate extractions were combined, dried (MgSO4), and concentrated in vacuo. Purification by silica gel chromatography (Waters Prep-500A) using hexane/ethyl acetate (25:75) gave 33 g (73%) of 1,4-dibutyl-1,3-dihydro-3-[(6-bromo-3-pyridinyl) methyl]-2H-imdazol-2-one as a reddish-brown waxy solid: NMR (CDCl3) δ 0.89 (t, J=7 Hz, 3H), 0.95 (t, J=7 Hz, 3H), 1.25-1.51 (m, 6H), 1.57-1.71 (m, 2H), 2.22 (t, J=8 Hz, 2H), 3.60 (t, J=7 Hz, 2H), 4.80 (s, 2H), 5.90 (S, 1H), 7.43 (d, J=9 Hz, 1H), 7.49 (dd, J=9 and 2 Hz, 1H), 8.24 (d, J=2Hz, 1H).

Workup

  1. temperatureto maintain the solution temperature below -20° C
  2. temperatureto slowly warm to ambient temperature overnight
  3. customThe reaction was partitioned between ethyl acetate and water
  4. washthe organic layer was washed twice with brine
  5. extractionthe combined aqueous phases were back-extracted with ethyl acetate
  6. extractionThe ethyl acetate extractions
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customPurification by silica gel chromatography (Waters Prep-500A)

Sources & evidence

ORD record
ord-26754b5407664914818e3fc0d6a2ecff
Source dataset
uspto-grants-1999_01
Patent number
US05861420

Reaction notes

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