Diisopropylamine → Ethyl 2-(furan-2-yl)-4-methyl-3-oxopentanoate

To 60 mL of tetrahydrofuran and 9.3 mL (66 mmol) of diisopropylamine, 38 mL (60 mmol) of 1.57 M n-butyllithium in n-hexane was added dropwise under a nitrogen atmosphere under cooling with ice, and the reaction mixture was warmed to room temperature and stirred for 30 minutes. After the stirring, the reaction mixture was cooled to −78° C., and after dropwise addition of 4.62 g (30.0 mmol) of ethyl 2-(furan-2-yl)acetate, stirred at the same temperature for 1 hour. After the stirring, 3.8 mL (36 mmol) of isobutyryl chloride was added at −78° C., and the reaction mixture was gradually warmed and then stirred at room temperature for 15 hours. After completion of the reaction, the reaction mixture was diluted with saturated aqueous ammonium chloride under cooling with ice and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate and with saturated aqueous sodium chloride successively, dried over anhydrous magnesium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by intermediate pressure silica gel column chromatography (silica gel 30 g, ethyl acetate:hexane=1:10) to give 22 g of the desired product as an orange liquid.

1. temperatureunder cooling with ice
2. temperatureAfter the stirring, the reaction mixture was cooled to −78° C.
3. stirringstirred at the same temperature for 1 hour
4. temperaturethe reaction mixture was gradually warmed
5. stirringstirred at room temperature for 15 hours
6. customAfter completion of the reaction
7. temperatureunder cooling with ice
8. extractionextracted with ethyl acetate
9. washThe organic layer was washed with saturated aqueous sodium hydrogen carbonate and with saturated aqueous sodium chloride successively
10. dry with materialdried over anhydrous magnesium sulfate
11. filtrationfiltered
12. concentrationthe filtrate was concentrated under reduced pressure
13. customThe resulting residue was purified by intermediate pressure silica gel column chromatography (silica gel 30 g, ethyl acetate:hexane=1:10)

ORD record

ord-d7a2b86c92114f8bba7f78ee06482e0d

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658686B2