反应详情

温度

-5 °C

A solution of diethyl zinc (500 mL, 1.0 M in hexanes) in methylene chloride (700 mL) was chilled to −10° C. under nitrogen in a cooling bath. A solution of trifluoroacetic acid (57 g, 0.5 mol) in methylene chloride (50 mL) was added dropwise over 1 hour 45 minutes. The mixture was stirred for 30 minutes at −5° C. A solution of diiodomethane (133.9 g, 0.5 mol) in methylene chloride (50 mL) was added to the mixture over a period of 20 minutes. The mixture became homogenous upon stirring for 30 minutes at 0° C. A solution of ethyl 2,2-difluoropent-4-enoate (40 g, 0.244 mol) in methylene chloride (50 mL) was added dropwise over a period of 25 minutes and the cooling bath was removed. The mixture was stirred for 1 hour at room temperature and then for 15 hours at reflux. The reaction was quenched by addition of saturated aqueous ammonium chloride (500 mL) and stirring for 30 minutes. The biphasic mixture was poured into 500 mL of saturated aqueous ammonium chloride and the organic layer was separated. The aqueous layer was extracted with methylene chloride (3×300 mL) and the combined organic extracts were dried over magnesium sulfate and filtered. The solvent was removed from the filtrate under reduced pressure to afford ethyl 3-cyclopropyl-2,2-difluoropropanoate (43.5 g, quant), as light yellow oil, which was used in the Example 4 without further purification. 1H-NMR (400 MHz, CDCl3): δ=0.12-0.22 (m, 2H), 0.49-0.59 (m, 2H), 0.75-0.91 (m, 1H), 1.37 (t, J=8 Hz, 3H), 1.95-2.05 (m, 2H), 4.34 (q, J=8 Hz, 2H).

1. stirringupon stirring for 30 minutes at 0° C
2. customthe cooling bath was removed
3. stirringThe mixture was stirred for 1 hour at room temperature
4. temperaturefor 15 hours at reflux
5. customThe reaction was quenched by addition of saturated aqueous ammonium chloride (500 mL)
6. stirringstirring for 30 minutes
7. additionThe biphasic mixture was poured into 500 mL of saturated aqueous ammonium chloride
8. customthe organic layer was separated
9. extractionThe aqueous layer was extracted with methylene chloride (3×300 mL)
10. dry with materialthe combined organic extracts were dried over magnesium sulfate
11. filtrationfiltered
12. customThe solvent was removed from the filtrate under reduced pressure