p-Toluenesulfonic acid → 3-(3,4-Dichlorophenyl)-3-oxo-1-propanol

Participants

Reaction Conditions

Reaction Steps

In 2.4 liters of ethanol, 119 g (0.46 mole) of ethyl 3-(3,4-dichlorophenyl)-3-oxopropionate were dissolved. To the resulting solution, 115 ml (0.68 mole) of ethyl orthoformate and 4.4 g (2.28 mmol) of p-toluenesulfonic acid were added, followed by heating under reflux for 8 hours. The reaction mixture was poured into 1 liter of a saturated aqueous solution of sodium bicarbonate and the mixture was extracted with ethyl acetate (700 ml, three times). The organic layers were combined, washed with a saturated aqueous solution of sodium chloride and then dried over anhydrous sodium sulfate. After the solvent was distilled off under reduced pressure, the residue was dissolved in 800 ml of tetrahydrofuran. The resulting solution was added dropwise to a suspension of 25.9 g (0.68 mole) of lithium aluminum hydride in 4 liters of tetrahydrofuran over 1 hour under ice-cooling. After stirring at 0° C. for 2 hours, 250 ml of water and 125 ml of a 10% aqueous solution of sodium hydroxide were added and the mixture was stirred at room temperature for a further 1 hour. The reaction mixture was filtered through Celite. The filtrate was poured into 1 liter of a saturated aqueous solution of sodium chloride, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. A residue was dissolved in 500 ml of chloroform. Under ice-cooling, 500 ml of 50% trifluoroacetic acid were added dropwise to the resulting solution over 30 minutes and the mixture was stirred for 30 minutes. The reaction mixture was diluted with 300 ml of methylene chloride. The organic layer was washed with water and a saturated aqueous solution of sodium bicarbonate and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by chromatography on a silica gel column (eluting solvent: n-hexane: ethyl acetate=9:1), whereby 46 g of the title compound were obtained as white crystals.

Provenance & Evidence