Diisopropylamine → ethyl (4S)-4-{[(benzyloxy)carbonyl]amino}-3-hydroxy-5-methylhexanoate

Temperature

-78 °C

Under an argon atmosphere, a solution (315 mL) of diisopropylamine (31.2 g) in dehydrated THF was cooled to −10° C., 1.6 mol/L butyllithium-hexane solution (175.3 mL) was added at −5° C. or below, and the mixture was stirred at the same temperature for 30 min. Then the mixture was cooled to −78° C., and a solution (65 mL) of ethyl acetate (24.7 g) in dehydrated THF was added dropwise at −70° C. or below. After stirring at the same temperature for 1 hr, a solution (70 mL) of benzyl [(1S)-1-formyl-2-methylpropyl]carbamate (16.5 g) in dehydrated THF was added dropwise at −65° C. or below. After stirring at −70° C. for 1 hr, acetic acid (36 g) was added, and the mixture was warmed to 0° C. The reaction mixture was poured into ice water, the mixture was extracted with ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=19/1→3/2) to give ethyl (4S)-4-{[(benzyloxy)carbonyl]amino}-3-hydroxy-5-methylhexanoate as colorless oil (yield: 15.4 g).

1. stirringAfter stirring at the same temperature for 1 hr
2. stirringAfter stirring at −70° C. for 1 hr
3. temperaturethe mixture was warmed to 0° C
4. extractionthe mixture was extracted with ethyl acetate
5. washthe organic layer was washed with saturated brine
6. dry with materialdried over anhydrous magnesium sulfate
7. concentrationconcentrated
8. customThe residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=19/1→3/2)

ORD record

ord-1a9926fd65ec4c30a6fd0444c6a61200

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08013008B2