Triethylamine → Methyl 4,4-difluoro-3-oxo-2-(piperidin-1-ylmethylidene)butyrate

Participants

Reaction Conditions

Reaction Steps

Methyl 3-piperidin-1-ylacrylate (96.7%, 50.7 g, 289 mmol) and triethylamine (31.07 g, 307 mol) were initially charged in toluene (300 ml) and cooled to −30° C. At this temperature, difluoroacetyl fluoride (30.1 g 307 mmol) was introduced. The reaction mixture was stirred at −30° C. for 3 h and then, over a period of 1 hour, warmed to room temperature. The reaction mixture was washed with deionized water (150 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 methyl 4,4-difluoro-3-oxo-2-(1-piperidin-1-ylmethylidene)butyrate as an orange oil (amount: 69.7 g; purity according to GC: 92.3%; yield: 90%). 1H-NMR (CDCl3): δ=1.75 (m, 6H), 3.3 (m, 2H), 3.62 (m, 2H), 3.75 (s, 3H), 6.62 (t, 1H), 7.89 ppm (s, 1H).

Provenance & Evidence