Toluene → 5-Butyl-4-methyldihydro-2(3H)-furanone, trans-

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Reaction Conditions

Reaction Steps

In 20 ml of anhydrous ether, 1.98 g of copper iodide (10.4 mmol) were suspended. To the obtained suspension, 20.8 ml of n-propyl lithium solution (1.0 N, 20.8 mmol) were added dropwise under an argon atmosphere with cooling at -50° C. Next, the resultant suspension was added dropwise into a mixture solution of 10 ml of anhydrous ether in which 1.97 g of tosylate (6.93 mmol) obtained in step [C] were dissolved, and 10 ml of toluene, under an argon atmosphere at -60° C. Next, the temperature of the reacted solution was raised from -60° C. to -20° C. over three hours. After that, the reacted solution was poured into a saturated aqueous ammonium chloride solution, then the obtained solution was stirred for thirty minutes, and filtered to remove insoluble substances. The obtained filtrate was extracted with ether, and the resultant extract was washed with water and a saturated aqueous sodium chloride solution, in this order. The resultant extract was then dried with anhydrous magnesium sulfate, and filtered. The filtrate was then concentrated. The obtained residue was dissolved in 20 ml of methanol, and 20 ml of 10% sodium hydroxide were added, and the solution was stirred at room temperature for three hours. After that, the methanol in the solution was distilled off under reduced pressure, the obtained residue was extracted twice with diethyl ether, and then the organic layer was separated from the obtained extract. Also, the residual aqueous layer was acidified with dilute hydrochloric acid, and extracted with diethyl ether five times. The obtained extract was combined with the organic layer as obtained before. The combined organic layer was dried with anhydrous magnesium sulfate, and concentrated to obtain the crude product. This crude product was purified via silica gel column chromatogrpahy (n-hexane:ether=10:1 to 2.1) and distilled under reduced pressure to obtain 763 mg of (3S,4R)-3-methyl-4-octanolide (trans-whisky lactone) (yield: 70.6%). This product exhibited the following properties:

Provenance & Evidence