反应详情

温度

-78 °C

To a solution (40 mL) of diisopropylamine (4.6 mL) in tetrahydrofuran was added 1.6 mol/L solution (20.19 mL) of n-butyllithium in hexane, and the mixture was cooled to −78° C. A solution (5 mL) of ethyl acetate (3.16 mL) in tetrahydrofuran was added dropwise to the mixture at a rate to maintain the reaction mixture at −70° C. or below. After the completion of the dropwise addition, the mixture was stirred at −78° C. for 1 hr, a solution (10 mL) of benzyl [(1S)-1-formyl-2-methylpropyl]carbamate (1.9 g) in tetrahydrofuran was added dropwise thereto at a rate to maintain the reaction mixture at −70° C. or below. The reaction mixture was once warmed to −30° C., and cooled again to −78° C. Acetic acid (2.3 mL) was added to the mixture, and the temperature of the mixture was raised to room temperature. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate=9:1→2:1) to give the title compound (yield: 800 mg) and ethyl (3R,4S)-4-{([(benzyloxy)carbonyl]amino}-3-hydroxy-5-methylhexanoate (yield: 550 mg) both as a colorless oil.

1. temperatureto maintain the reaction mixture at −70° C. or below
2. additionAfter the completion of the dropwise addition
3. temperatureat a rate to maintain the reaction mixture at −70° C. or below
4. temperatureThe reaction mixture was once warmed to −30° C.
5. temperaturecooled again to −78° C
6. temperaturethe temperature of the mixture was raised to room temperature
7. extractionthe mixture was extracted with ethyl acetate
8. washThe extract was washed with saturated brine
9. dry with materialdried over anhydrous sodium sulfate
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate=9:1→2:1)