Methanol → (2S,4E)-6-(Benzyloxy)-2-isopropylhex-4-enoic acid

Participants

Reaction Steps

94 ml of a solution of n-butyllithium in n-hexane (1.57 mol/l) (148 mmol) was added to a solution of 23 ml of diisopropylamine (163 mmol) in tetrahydrofuran (265 ml) under a nitrogen atmosphere and under ice-cooling over 45 minutes. The mixture was stirred at the same temperature for 20 minutes to prepare a solution of lithium diisopropylamide in tetrahydrofuran. A solution of 34.95 g of 3-methylbutanoic acid (1R)-1-[(benzyloxy)methyl]prop-2-en-1-yl ester obtained in Example (1a) (133 mmol) in tetrahydrofuran (70 ml) was added to the solution above under cooling in a dry ice-acetone bath over 40 minutes, and the mixture was stirred at the same temperature for 20 minutes. Then, 39 ml of trimethylsilyl chloride (307 mmol) was added to the reaction mixture over 20 minutes. The mixture was stirred at the same temperature for 20 minutes and then further stirred at room temperature for three hours. After cooling in an ice bath, 27 ml of methanol (667 mmol) was added to the reaction mixture so that the internal temperature did not exceed 20° C. The mixture was further stirred at room temperature for one hour. The reaction mixture was concentrated under reduced pressure and diluted with 270 ml of a 1 M sodium hydroxide aqueous solution, followed by extraction with t-butyl methyl ether. Then, the organic layer was washed with 68 ml of a 1 M sodium hydroxide aqueous solution. All aqueous layers were combined and made acidic with 78 ml of 6 M hydrochloric acid, followed by extraction with ethyl acetate. Then, the organic layer was washed with water and brine and dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure to obtain 19.03 g of the crude title compound.

Provenance & Evidence