Diethyl Ether → Ethyl 2-cyclopentyl-2-hydroxy-2-phenylacetate

Beteiligte Stoffe

Reaktionsschritte

Into a solution of 23.5 g of phenylglyoxylic acid ethyl ester in 200 ml of tetrahydrofuran, a diethyl ether solution of cyclopentyl magnesium chloride was added dropwise under ice cooling, followed by 30 minutes' stirring at the same temperature. Saturated aqueous ammonium chloride solution was added to the reaction mixture, and the reaction product was extracted with ethyl acetate, washed with saturated saline solution, and dried over anhydrous magnesium sulfate. Distilling the solvent off, the residue was purified by silica gel column chromatography (hexane/ethyl acetate=30/1 to 20/1). Thus 11 g of 2-cyclopentyl-2-hydroxy-2-phenylacetic acid ethyl ester was obtained, which was dissolved in 40 ml of methanol. To the solution 20 ml of 4N sodium hydroxide solution was added at room temperature, followed by 2 hours' stirring at the same temperature, and 1 hour's stirring at 50° C. Distilling the methanol off under reduced pressure, the aqueous layer was rendered weakly acidic with 4N hydrochloric acid and then extracted with ethyl acetate. The extract was washed with saturated saline solution, dried over anhydrous sodium sulfate and removed of the solvent by distillation. The resulting solid was washed with diethyl ether/hexane=1/1, and 8.7 g of 2-cyclopentyl-2-hydroxy-2-phenylacetic acid was obtained, which was dissolved, together with 11.6 g of cinchonidine, in 1.5 liters of toluene under heating, and the solution was cooled off to room temperature consuming about 4 hours. The white needles whereby precipitated were once again dissolved in 900 ml of toluene and cooled off to room temperature consuming about 4 hours. Recovering the precipitated white, acicular crystals by filtration, 8.0 g of (2R)-2-cyclopentyl-2-hydroxy-2-phenylacetic acid cinchonidine salt was obtained. The salt was dissolved in a mixture of diethyl ether and 1N hydrochloric acid, and the organic layer was washed with water and then with saturated saline solution, and dried over anhydrous magnesium sulfate. Distilling the solvent off under reduced pressure, 3.0 g of the title compound was obtained as a white solid

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