Hydrochloric Acid → 2-(1-{[2-(phenyloxy)phenyl]methyl}-1H-pyrazol-3-yl)-1H-isoindole-1,3(2H)-dione

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Reaction Steps

A solution of 2-(1H-pyrazol-3-yl)-1H-isoindole-1,3(2H)-dione (for a preparation see Intermediate 28)(3.08 g, 14.4 mmol) in THF (30 ml) under nitrogen, was treated with 1.0 M lithium bis(trimethylsilyl)amide in THF (15.9 ml, 15.9 mmol, Aldrich) and stirred at room temperature for 15 min. 1-(Bromomethyl)-2-(phenyloxy)benzene (3.8 g, 14.4 mmol, Maybridge) in THF (10 ml) was added and the mixture stirred overnight. The mixture was diluted with DCM (50 ml) and water (50 ml). To the emulsion was added brine (30 ml) and diluted aqueous HCl (15 ml). The resulting phases were separated and the aqueous layer was further extracted with DCM (50 ml). The combined organic extracts were filtered through a hydrophobic frit and the filtrate concentrated under reduced pressure. The residue was loaded in dichloromethane and purified on silica 330 g using 0-50% ethyl acetate-dichloromethane. The appropriate fractions were combined and evaporated in vacuo to give 2-(1-{[2-(phenyloxy)phenyl]methyl}-1H-pyrazol-3-yl)-1H-isoindole-1,3(2H)-dione as an off-white gum (2.35 g).

Provenance & Evidence