Diisopropylamine → (4R,5R)-4,5-Dimethyl-3-oxo-octanoic acid

Temperature

-78 °C

To a solution containing 2.0 g (13.9 mmol) of (2R,3R)-2,3-dimethyl-hexanoic acid in 20 mL of dichloromethane was added 2.1 g (16.6 mmol) of chloromethylene dimethyl-ammonium chloride. After stirring the resulting solution under nitrogen for 1.5 hours, the solvent was evaporated to give (2R,3R)-2,3-dimethyl-hexanoyl chloride. Butyl lithium (32.7 ml, 52.4 mmol) was added to a solution of diisopropylamine (4.9 g, 48.5 mmol) in dry THF (20 mL) under nitrogen at 0° C. and stirred for 20 minutes. The solution was cooled to −78° C. and 4.3 g (48.5 mmol) of ethyl acetate was added. The solution was stirred at that temperature for 45 minutes. (2R,3R)-2,3-Dimethyl-hexanoyl chloride in dry THF (20 mL) was slowly added to the ethyl acetate enolate at −78° C. and the resulting reaction mixture was allowed to warm to room temperature. The reaction mixture was stirred at room temperature for 2.5 hours and was cooled to 0° C. The reaction was 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 2.7 g (89.2% yield) of the titled compound as an oil.

1. stirringThe solution was stirred at that temperature for 45 minutes
2. customthe resulting reaction mixture
3. temperatureto warm to room temperature
4. stirringThe reaction mixture was stirred at room temperature for 2.5 hours
5. temperaturewas cooled to 0° C
6. customThe reaction was quenched with a saturated solution of ammonium chloride
7. extractionextracted into ethyl acetate
8. washThe solution was washed with brine
9. dry with materialdried over MgSO4
10. concentrationconcentrated
11. filtrationThe resulting residue was filtered through a silica plug
12. washeluting with 60/40 solution of hexane/ethyl acetate

ORD record

ord-7553142cb1a7474b8ae872a2e291a145

Source dataset

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07179934B2