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

HRID 1946548Notes

Reaction equation

HRID 1946548 reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([I:9])[CH:4]=1.[CH3:10][CH:11]([C:13]1[NH:17][C:16]2[CH2:18][CH2:19][CH2:20][C:21](=[O:22])[C:15]=2[N:14]=1)[CH3:12]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1.[OH-].[Na+].ClCCl>[I:9][C:5]1[CH:4]=[C:3]([CH2:2][N:14]2[C:15]3[C:21](=[O:22])[CH2:20][CH2:19][CH2:18][C:16]=3[N:17]=[C:13]2[CH:11]([CH3:12])[CH3:10])[CH:8]=[CH:7][CH:6]=1

Participants

7

Reactant 2

HCID 27593613-Iodobenzyl bromide2×HCID 584601782-Isopropyl-5,6-dihydro-1H-benzo[d]imidazol-7(4H)-one

Product 1

HCID 584601523-[(3-iodophenyl)methyl]-2-(1-methylethyl)-3,5,6,7-tetrahydro-4H-benzimidazol-4-oneYield 53.7%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 14798Sodium HydroxideSolvent

Procedure

1-(bromomethyl)-3-iodobenzene (9.76 g) was added to a stirred solution of tetrabutylammonium bromide (4.41 g), Intermediate 56 (2nd alternative preparation) (4.88 g) and 1-(bromomethyl)-3-iodobenzene (9.76 g) in Toluene (100 mL) and NaOH (5M, Aq) (46.5 mL). The reaction mixture was allowed to stir vigorously, so as to ensure mixture of the 2 phases, at room temperature for 2.75 hr. The reaction mixture was partitioned between DCM (80 mL) and water (80 mL) and aqueous layer was washed with further DCM (2×80 mL). The organic layers were combined, filtered through a hydrophobic frit and concentrated in vacuo to give 16.84 g of crude product as a brown oil. 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 products 5.8 g as a yellow oil which solidified. LC/MS MH+ 394, Rt 2.85 min (5 min run).

Workup

  1. additionmixture of the 2 phases
  2. customThe reaction mixture was partitioned between DCM (80 mL) and water (80 mL) and aqueous layer
  3. washwas washed with further DCM (2×80 mL)
  4. filtrationfiltered through a hydrophobic frit
  5. concentrationconcentrated in vacuo
  6. customto give 16.84 g of crude product as a brown oil
  7. custompurified by column chromatography (silica)
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-047ceeb9ae2a476997684b7f9a44e55b
Source dataset
uspto-grants-2013_03
Patent number
US08399444B2

Reaction notes

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