Diisopropylamine → HCID 14131463, compound

To a solution of N-[(benzyloxy)carbonyl]-L-valine (25.0 g) in dry THF (100 mL) was added 1,1′-carbonylbis-1H-imidazole (19.4 g) at 0° C. in small portions, and the mixture was stirred at room temperature overnight (solution 1). To a solution of diisopropylamine (30.2 g) in dry THF (330 mL) was added dropwise a 1.6 mol/L n-butyllithium-hexane solution (186.5 mL) under an argon atmosphere at −78° C. and the mixture was stirred for 30 min, and a solution of ethyl acetate (29.2 mL) in dry THF (100 mL) was added dropwise thereto. The mixture was stirred at −78° C. for 30 min and solution 1 was added dropwise and, after the completion of the dropwise addition, the mixture was further stirred at −78° C. for 1 hr. Acetic acid (25 mL) was added to the reaction mixture, and the mixture was warmed to room temperature. Water was added and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=50:1→1:1) to give ethyl 4-{[(benzyloxy)carbonyl]amino}-5-methyl-3-oxohexanoate as a colorless oil (yield: 24.0 g, 75%). To a solution (150 mL) of ethyl 4-{[(benzyloxy)carbonyl]amino}-5-methyl-3-oxohexanoate (12.0 g) in acetone were added potassium carbonate (10.3 g) and iodomethane (7.0 mL), and the mixture was refluxed overnight. After allowing to room temperature, water was added and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=50:1→1:1) to give the title compound as a colorless oil (yield: 7.35 g, 56%).

1. stirringThe mixture was stirred at −78° C. for 30 min
2. additionafter the completion of the dropwise addition
3. stirringthe mixture was further stirred at −78° C. for 1 hr
4. extractionthe mixture was extracted with ethyl acetate
5. washThe extract was washed with saturated brine
6. dry with materialdried over magnesium sulfate
7. concentrationconcentrated under reduced pressure
8. customThe obtained residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=50:1→1:1)

ORD record

ord-e3755fd457ad4a21b6567e42d2c31eec

Source dataset

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07834051B2