Triethylamine → (4R,5R)-4,5-Dimethyl-3-oxo-octanoic Acid Ethyl Ester

To a solution containing 1.0 g (6.9 mmol) of (2R,3R)-2,3-dimethyl-hexanoic acid in 10 mL of dichloromethane was added 1.1 g of chloromethylene dimethyl-ammonium chloride (8.3 mmol). The resulting solution was stirred under nitrogen for 1.5 hours. The solvent was subsequently evaporated to give (2R,3R)-2,3-dimethyl-hexanoyl chloride. To a solution containing 2.5 g (14.6 mmol) of potassium monoethyl malonate in 50 mL of acetonitrile was added 1.7 g (17.3 mmol) of magnesium chloride and 1.2 g (11.4 mmol) of triethylamine. The resulting mixture was stirred at room temperature for 2.5 hours. The reaction was cooled to 0° C. and a solution of the (2R,3R)-2,3-dimethyl-hexanoyl chloride in acetonitrile (20 mL) was slowly added followed by the addition of triethylamine (0.4 g, 0.4 mmol). The reaction was heated to 40° C. and stirred at that temperature for 6 hours. The reaction mixture was cooled to 25° C., quenched with a saturated solution of ammonium chloride and extracted into ethyl acetate. The solution was washed with brine, dried over MgSO4 and concentrated. The resulting residue was filtered through a silica plug, eluting with 60/40 solution of hexane/ethyl acetate to afford 1.3 g (87.8% yield) of the titled compound as an oil.

1. temperatureThe reaction was cooled to 0° C.
2. temperatureThe reaction was heated to 40° C.
3. stirringstirred at that temperature for 6 hours
4. temperatureThe reaction mixture was cooled to 25° C.
5. customquenched with a saturated solution of ammonium chloride
6. extractionextracted into ethyl acetate
7. washThe solution was washed with brine
8. dry with materialdried over MgSO4
9. concentrationconcentrated
10. filtrationThe resulting residue was filtered through a silica plug
11. washeluting with 60/40 solution of hexane/ethyl acetate

ORD-Eintrag

ord-30cb0f2eed5c4aefb61b601963a8eb8c

Quelldatensatz

uspto-grants-2008_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07388023B2