Potassium Fluoride → Ethyl 4,4-difluoro-3-oxo-2-(piperidin-1-ylmethylidene)butyrate

Temperature

-30 °C

Ethyl 3-piperidin-1-ylacrylate (99%, 8.7 g, 50 mmol) and KF (spray dried) (4.44 g, 76.3 mmol) were initially charged in 100 ml of toluene and cooled to −30° C. At this temperature, difluoroacetyl fluoride (98%, 6.10 g, 61 mmol) was then introduced. The reaction mixture was stirred at −30° C. for 3 h and then, over a period of 1 h, warmed to room temperature. The reaction mixture was washed with deionized water (50 ml). After separation of the phases, the aqueous phase was extracted once with toluene (100 ml). The toluene phases were combined and washed with an aqueous saturated NaCl solution (100 ml), and the solvent was then removed under reduced pressure. This gave ethyl 4,4-difluoro-3-oxo-2-(1-piperidin-1-ylmethylidene)butyrate as an orange oil (amount: 13.0 g; purity according to GC: 91.2%; yield: 94%). 1H-NMR (CDCl3): δ=1.3 (t, 3H), 1.75 (m, 6H), 3.3 (m, 2H), 3.6 (m, 2H), 4.25 (q, 2H), 6.6 (t, 1H), 7.85 ppm (s, 1H).

1. waitover a period of 1 h
2. temperaturewarmed to room temperature
3. washThe reaction mixture was washed with deionized water (50 ml)
4. customAfter separation of the phases
5. extractionthe aqueous phase was extracted once with toluene (100 ml)
6. washwashed with an aqueous saturated NaCl solution (100 ml)
7. customthe solvent was then removed under reduced pressure

ORD record

ord-b4763bc487654260b703e7a48ff8e93f

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08586750B2