Sodium Hydroxide → 3-[(4-iodophenyl)methyl]-2-(1-methylethyl)-3,5,6,7-tetrahydro-4H-benzimidazol-4-one

HRID 1946545Notes

Reaction equation

HRID 1946545 reaction equation
[CH3:1][CH:2]([C:4]1[NH:8][C:7]2[CH2:9][CH2:10][CH2:11][C:12](=[O:13])[C:6]=2[N:5]=1)[CH3:3].Br[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([I:22])=[CH:18][CH:17]=1.[OH-].[Na+]>C1(C)C=CC=CC=1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[I:22][C:19]1[CH:20]=[CH:21][C:16]([CH2:15][N:5]2[C:6]3[C:12](=[O:13])[CH2:11][CH2:10][CH2:9][C:7]=3[N:8]=[C:4]2[CH:2]([CH3:1])[CH3:3])=[CH:17][CH:18]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 9542584-Iodobenzyl bromideHCID 584601782-Isopropyl-5,6-dihydro-1H-benzo[d]imidazol-7(4H)-one

Product 1

HCID 584602073-[(4-iodophenyl)methyl]-2-(1-methylethyl)-3,5,6,7-tetrahydro-4H-benzimidazol-4-oneYield 55.7%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolvent

Procedure

To Intermediate 56 (2nd alternative preparation) (5.4 g) in Toluene (120 mL) was added 1-(bromomethyl)-4-iodobenzene (9.00 g) and tetrabutylammonium bromide (4.88 g) then sodium hydroxide, 5M aq (66.7 mL). The mixture was then stirred at room temperature, stirring vigorously to mix the phases for 1.5 h. The mixture was partitioned between ethyl acetate and water. The brown solid was filtered. The 2 phases were separated and the aqueous layer extracted well with ethyl acetate. The combined organics were dried (hydrophobic frit) and evaporated. The sample was loaded in dichloromethane and purified by column chromatography (silica) using 0-100% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the required product 6.65 g as a brown oil. LC/MS MH+ 395, Rt 2.88 min (5 min run).

Workup

  1. stirringstirring vigorously
  2. additionto mix the phases for 1.5 h
  3. customThe mixture was partitioned between ethyl acetate and water
  4. filtrationThe brown solid was filtered
  5. customThe 2 phases were separated
  6. extractionthe aqueous layer extracted well with ethyl acetate
  7. customThe combined organics were dried (hydrophobic frit)
  8. customevaporated
  9. custompurified by column chromatography (silica)
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-e7ebde722fe740b8bd6b03202d3349e9
Source dataset
uspto-grants-2013_03
Patent number
US08399444B2

Reaction notes

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