4-Methoxybenzoic Acid → LY88074 Trimethyl ether

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Reaction Steps

4-Methoxybenzoic acid (450 mg, 2.96 mmol), thionyl chloride (3 ml, 44.4 mmol) and anhydrous dimethylformamide (1 drop) were added to anhydrous chloroform (10 ml), and the resulting mixture was refluxed for 3 hours under argon atmosphere and then cooled to room temperature. After the reaction mixture was concentrated under reduced pressure, the residue was dissolved in anhydrous dichloromethane, and 6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene (760 mg, 2.8 mmol) synthesized by the method described in J. Med. Chem. 1057(1984) and aluminum chloride (2.37 g, 17.76 mmol) were added to the resulting solution followed by stirring for 4 hours at room temperature. Tetrahydrofuran and ice were added to stop the reaction and the reaction mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate. After distilling off the solvent, the filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel column chromatography (eluent: dichloromethane/hexane=1/1) to give [6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophen-3-yl](4-methoxy-phenyl)-methanone (405 mg, Yield 39%) as a yellow oil.

Provenance & Evidence