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

HRID 1946522Notes

Reaction equation

HRID 1946522 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]([Cl:22])=[CH:18][CH:17]=1.[OH-].[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[Cl: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 693291-(Bromomethyl)-4-chlorobenzeneHCID 584601782-Isopropyl-5,6-dihydro-1H-benzo[d]imidazol-7(4H)-one

Product 1

HCID 584601493-[(4-chlorophenyl)methyl]-2-(1-methylethyl)-3,5,6,7-tetrahydro-4H-benzimidazol-4-oneYield 60.4%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolvent

Procedure

To a stirred suspension of Intermediate 56 (867 mg), 1-(bromomethyl)-4-chlorobenzene (1100 mg) and tetrabutylammonium bromide (784 mg) in toluene (20 mL) at ambient temperature was added aqueous sodium hydroxide 20% wt (9 mL). The reaction was stirred at ambient temperature for 2 hr. The reaction was quenched with saturated aqueous ammonium chloride (50 mL) and extracted with ethyl acetate (2×50 mL). The combined organics were dried (hydrophobic frit) and concentrated in vacuo. The sample was loaded in dichloromethane and purified on silica using a 0-100% ethyl acetate-cyclohexane gradient. The appropriate fractions were combined and evaporated in vacuo to give the required product (0.89 g). LC/MS MH+ 303, Rt 2.02 min (5 min run).

Workup

  1. customThe reaction was quenched with saturated aqueous ammonium chloride (50 mL)
  2. extractionextracted with ethyl acetate (2×50 mL)
  3. customThe combined organics were dried (hydrophobic frit)
  4. concentrationconcentrated in vacuo
  5. custompurified on silica using a 0-100% ethyl acetate-cyclohexane gradient
  6. customevaporated in vacuo

Sources & evidence

ORD record
ord-e4252d7c2b7048cd9f82b3b621385166
Source dataset
uspto-grants-2013_03
Patent number
US08399444B2

Reaction notes

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