Benzyl Bromide → 4'-Benzyloxy-2'-hydroxypropiophenone

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Reaction Steps

A mixture of 5.0 g of 2',4'-dihydroxypropiophenone, 5.4 g of benzyl bromide, 6.2 g of potassium carbonate and 50 ml of acetone was refluxed for 7 hours. After cooling, the solid was separated by filtration. The filtrate was concentrated, and the residue was separated by column chromatography to give 4.7 g of 4'-benzyloxy-2'-hydroxypropiophenone as a white solid (yield 61%, melting point 111.5°-112.5° C.). Then, a mixture of 4.5 g of this solid, 3.5 g of ethyl bromoacetate, 6.1 g of potassium carbonate and 45 ml of acetone was refluxed for 7.5 hours. After cooling, the solid was separated by filtration. The filtrate was concentrated, and the residue was purified by column chromatography to give 5.8 g of ethyl 3-benzyloxy-6-propionylphenoxyacetate as white crystals (yield 97%, melting point 81.5° to 82.0° C.). This ester (5.5 g) was dissolved in a solution composed of 1.3 g of potassium hydroxide and 55 ml of methanol, and the solution was stirred at room temperature for 2 hours to hydrolyze the ester. The hydrolysis product was worked up in a customary manner to give 3.9 g (yield 77%) of 3-benzyloxy-6-propionylphenoxyacetic acid as a pale yellowish orange solid. Then, 9.3 g of sodium acetate and 39 ml of acetic anhydride were added to this solid, and the mixture was heated at 155° C. for 30 minutes. The solvent was evaporated, and the residue was purified by column chromatography to give 2.8 g (yield 95%, melting point 69.5°-70.5° C.) of 6-benzyloxy-3-ethylbenzofuran as a white solid. Palladium (5%)-carbon (0.27 g) and 27 ml of acetic acid were added to 2.7 g of the resulting benzofuran, and the mixture was stirred at room temperature for 3 hours in an atmosphere of nitrogen. The catalyst was separated by filtration, and the filtrate was concentrated and then purified by column chromatography to give 1.7 g (yield 90%) of the desired product as a pale orange liquid.

Provenance & Evidence