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

HRID 1946540Notes

Reaction equation

HRID 1946540 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])=[C:18]([Cl:23])[CH:17]=1.[OH-].[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[Cl:23][C:18]1[CH:17]=[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:21]=[CH:20][C:19]=1[Cl:22]

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 6397264-(Bromomethyl)-1,2-dichlorobenzeneHCID 584601782-Isopropyl-5,6-dihydro-1H-benzo[d]imidazol-7(4H)-one

Product 1

HCID 584601653-[(3,4-dichlorophenyl)methyl]-2-(1-methylethyl)-3,5,6,7-tetrahydro-4H-benzimidazol-4-one

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolvent

Procedure

To Intermediate 56 (1st Alternative preparation) (88.83 g, product of multiple previous experiments) was added toluene (2000 mL) followed by 4-(bromomethyl)-1,2-dichlorobenzene (132 g) and tetrabutylammonium bromide (80 g) then sodium hydroxide (1096 mL). The mixture was then stirred at room temperature, stirring vigorously to mix the phases. The temp rose by 5° C. over 5 mins. After 1.5 hr the mixture was partitioned between ethyl acetate and water and the aqueous layer extracted well with ethyl acetate—aq phase got up to 50° C. The combined organics were washed with water, brine, dried (MgSO4), filtered and evaporated. The crude product was purified by column chromatography, loaded in DCM, eluting with 0-100% ethyl acetate in cyclohexane. The appropriate fractions were evaporated and this gave the title compound, a cream solid, two batches 114.8 gm and 16.22 gm. LC/MS MH+337, 339, Rt 0.96 min (2 min run).

Workup

  1. stirringstirring vigorously
  2. additionto mix the phases
  3. customAfter 1.5 hr the mixture was partitioned between ethyl acetate and water
  4. extractionthe aqueous layer extracted well with ethyl acetate—aq phase
  5. customgot up to 50° C
  6. washThe combined organics were washed with water, brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customevaporated
  10. customThe crude product was purified by column chromatography
  11. washeluting with 0-100% ethyl acetate in cyclohexane
  12. customThe appropriate fractions were evaporated

Sources & evidence

ORD record
ord-f8a0a95b509a4be8b5305523a308d516
Source dataset
uspto-grants-2013_03
Patent number
US08399444B2

Reaction notes

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