Ethyl Acetate → 1-Cyclopropyl-butane-1,3-dione

Temperature

60 °C

To a a stirring solution of THF (100 mL) was suspended potassium tert-butoxide (5.60 g, 49.5 mmol), followed by a mixture of cyclopropyl methyl ketone (3.27 mL, 33 mmol) and ethyl acetate (9.69 mL, 99 mmol) in 30 mL THF at 35° C., via addition funnel over a 25 min period. The contents were heated and stirred at 60° C. After 3 h, the contents were removed from heating, and allowed to stir with cooling to room temperature. The reaction mixture was carefully diluted with 30 mL 2N HCl and stirred for 10 min. The mixture was extracted with diethyl ether (3×50 mL), and the combined organic layers washed with brine (1×50 mL). The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The crude oil was chromatographed on silica gel (eluent: 0 to 15% EtOAc in hexanes) with good separation to afford the desired product as a light yellow colored oil, 3.9 g in ˜75% purity (residual solvent), for an overall yield of 70%. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.89-0.96 (m, 2 H), 1.09-1.15 (m, 2 H), 1.59-1.69 (m, 1H), 2.04 (s, 3H), 5.63 (s, 1 H), 15.5-16.0 (br s, 1H).

1. temperatureThe contents were heated
2. customthe contents were removed
3. temperaturefrom heating
4. stirringto stir
5. temperaturewith cooling to room temperature
6. additionThe reaction mixture was carefully diluted with 30 mL 2N HCl
7. stirringstirred for 10 min
8. extractionThe mixture was extracted with diethyl ether (3×50 mL)
9. washthe combined organic layers washed with brine (1×50 mL)
10. dry with materialThe organic layer was dried over MgSO4
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customThe crude oil was chromatographed on silica gel (eluent: 0 to 15% EtOAc in hexanes) with good separation

ORD record

ord-9c58baca0abb4327a4684900f205dd80

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09073924B2