Acetic Acid → HCID 178454384, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of diisopropylamine (418 mg, 4.15 mmol) in anhydrous tetrahydrofuran (6 mL) under the atmosphere of argon was added a 1.58 M n-butyl lithium-hexane solution (2.5 mL, 5.4 mmol) with stirring under ice cooling, and the mixture was stirred at 0° C. for 10 min, and then at −78° C. for 5 min. A solution of trans-4-benzyloxycarbonylmethyl-1-t-butyldimethylsilyloxycyclohexan (1.36 g, 3.76 mmol) in anhydrous tetrahydrofuran (7 mL) was added dropwise at the same temperature over 7 min, and the reaction mixture was further stirred for 15 min. The cold enolate solution thus prepared was added dropwise via canula to a solution of benzyl 3-methyl-2-ketobutyrate (776 mg, 3.76 mmol) in anhydrous tetrahydrofuran (4 mL) having been cooled to −78° C. After stirring at −78° C. for 1 h, the reaction mixture was adjusted to pH 4 with acetic acid, and the temperature was raised to room temperature. The reaction solvent was evaporated under reduced pressure, and the residue was diluted with ethyl acetate and water to separate the phases for extraction. The aqueous layer was extracted again with ethyl acetate, and the combined organic layer was concentrated under reduced pressure and the residue thus obtained was subjected to silica gel column chromatography (hexane-ethyl acetate 20:1) to give dibenzyl 3-(trans-4-t-butyldimethylsilyloxycyclohexyl)-2-hydroxy-2-isopropylsuccinate as oil in amounts of 629 mg (low polar diastereomer, yield: 29%) and 801 mg (high polar diastereomer, yield: 37%), respectively.

Provenance & Evidence