6-(2-Quinolinylmethoxy)-2-methyl-1-indanone → 2-Methyl-5-(2-quinolinylmethoxy)-indene-3-acetic acid ethylester

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Reaction Steps

Triethylphosphonoacetate (22.41 g, 100 mmole) is added dropwise under nitrogen to a stirred and cooled (0° C.) slurry of Nail (57% in oil, 4.27 g, 100 mmole) in dry toluene (250 mL). The cooling bath is removed and stirring continued at room temperature for 60 minutes whereby an almost homogeneous solution is obtained. A solution of the indanone (15.15 g, 50 mmole) of Step E, in toluene (50 mL) is then added dropwise. The flask is placed in an oil bath heated at 95° C. for 19 hours (TLC, traces of starting material present, dichloromethane-ethyl acetate 9:1, UV, Vaughn's). The reddish solution is cooled, diluted with water and extracted with ethyl acetate (3 times). The combined extracts are washed with brine, dried (anhydrous K2CO3) and evaporated to dryness. The residue (heavy brown oil) is flash chromatographed (on silica Merck-60, eluted using a gradient dichloromethane AE dichloromethane:ethyl acetate 84:16) to provide the title compound as a mixture of endo and exo isomers (16.3 g, 87.4%, oil that solidifies upon standing) together with unreacted, more polar starting material (1.84 g, 12% recovery).

Provenance & Evidence