Toluene → 3-[(4-chlorophenyl)methyl]-2-(1-methylethyl)-5,6,7,8-tetrahydrocyclohepta[d]imidazol-4(3H)-one

HRID 1946468Notes

Reaction equation

HRID 1946468 reaction equation
[CH3:1][CH:2]([C:4]1[NH:8][C:7]2[CH2:9][CH2:10][CH2:11][CH2:12][C:13](=[O:14])[C:6]=2[N:5]=1)[CH3:3].[Cl:15][C:16]1[CH:23]=[CH:22][C:19]([CH2:20]Br)=[CH:18][CH:17]=1.C1(C)C=CC=CC=1.[NH4+].[Cl-]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.[OH-].[Na+]>[Cl:15][C:16]1[CH:23]=[CH:22][C:19]([CH2:20][N:5]2[C:6]3[C:13](=[O:14])[CH2:12][CH2:11][CH2:10][CH2:9][C:7]=3[N:8]=[C:4]2[CH:2]([CH3:1])[CH3:3])=[CH:18][CH:17]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 25517Ammonium ChlorideHCID 693291-(Bromomethyl)-4-chlorobenzeneHCID 584602222-(1-methylethyl)-5,6,7,8-tetrahydrocyclohepta[d]imidazol-4(1H)-one

Product 1

HCID 584602263-[(4-chlorophenyl)methyl]-2-(1-methylethyl)-5,6,7,8-tetrahydrocyclohepta[d]imidazol-4(3H)-oneYield 45.5%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 14798Sodium HydroxideSolvent

Procedure

Tetrabutylammonium bromide (1.7 g) was added to a stirred mixture of Intermediate 2 (2 g) and 4-chlorobenzyl bromide (2.4 g) in sodium hydroxide 20% aq. (14.2 mL) and Toluene (7 mL). The RM was stirred at room temp under nitrogen atm for 3 hours. An excess of sat NH4Cl aq. solution was added and the mixture was extracted with EtOAc (3×30 ml). The organics were combined, dried (hydrophobic frit) and concentrated under vacuum. The residue was purified on silica using a cyclohexane:ethyl acetate 0-100% gradient. The desired fractions were combined and concentrated under vacuum to give the title compound (1.5 g). LC/MS MH+ 317, Rt 1.91 min (5 minute run).

Workup

  1. extractionthe mixture was extracted with EtOAc (3×30 ml)
  2. customdried (hydrophobic frit)
  3. concentrationconcentrated under vacuum
  4. customThe residue was purified on silica using a cyclohexane
  5. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-297eec495c88479f9059138b8cecef72
Source dataset
uspto-grants-2013_03
Patent number
US08399444B2

Reaction notes

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