1-Bromo-2-methyl-1-propene → Trans-eldanolide

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Reaction Conditions

Reaction Steps

500 mg (3.47 mmol) of the epoxide obtained in Example 2 [C'] were dissolved in 10 ml of anhydrous tetrahydrofuran. To the resultant solution, 49.8 mg (0.35 mmol) of copper bromide were further added. To the obtained mixture, Grignard reagent which had been prepared by utilizing 2-methyl propenyl bromide (2.34 g, 17.4 mmol) and magnesium (842 mg, 34.7 mmol) was slowly added dropwise under an argon atmosphere with cooling at -20° C. When the disappearance of the epoxide was confirmed by a gas chromatography, dropwise addition of the Grignard reagent was terminated. The reacted solution was poured into a saturated aqueous ammonium chloride solution, followed by extraction with diethyl ether. The obtained extract was washed with water and saturated sodium chloride aqueous solution, in this order, and dried with anhydrous sulfate. The extract was then filtered, and the filtrate was concentrated. The obtained residue wa dissolved in 10 m of methanol. The resultant solution was added to 10 ml of 10% aqueous sodium hydroxide solution, followed by stirring at room temperature for three hours. Next, methanol in the solution was distilled off under reduced pressure, and the obtained residue was extracted twice with diethyl ether and then the organic layer was separated from the obtained extract. Also, the obtained aqueous layer was acidified with dilute hydrochloric acid, and extracted five times with diethyl ether. The obtained extract was combined with the organic layer obtained before. The combined organic layer was dried with anhydrous magnesium sulfate, and concentrated to obtain a crude product. This crude product was purified via silica gel column chromatography (n-hexane:ethyl acetate=10:1 to 5:1), and distilled under reduced pressure to obtain 430 mg of (3S,4R)-3,7-dimethyl-6-octen-4-olide (eldanolide) (yield: 73.8%). This product exhibited the following physical properties:

Provenance & Evidence