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

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Reaction Steps

Tetrabutylammonium bromide (1.33 g) was added to a stirred mixture of Intermediate 13 (1.7 g), 4-chlorobenzyl bromide (1.86 g) in sodium hydroxide 20% aq. (12 mL) and toluene (6 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 crude material. It was purified by reverse phase chromatography using an acetonitrile-0.1% NH3:water—with an amonium carbonate buffer modifier (pH=10) 5%-95% gradient. The desired fractions were combined and concentrated under vacuum to yield the title compound (650 mg). LC/MS MH+ 331 Rt 2.04 min (5 minute run).

Provenance & Evidence