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

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence