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

Temperatur

-30 °C

Methyl 3-piperidin-1-ylacrylate (99%, 8.7 g, 51 mmol) and pyridine (4.26 g, 54 mmol) was initially charged in toluene (150 ml) and cooled to −30° C. At this temperature, difluoroacetyl fluoride (10 g, 61 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 (200 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: 12.0 g; purity according to GC: 97.7%; yield: 93.2%).

1. waitover a period of 1 hour
2. temperaturewarmed to room temperature
3. washThe reaction mixture was washed with deionized water (200 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-Eintrag

ord-fde1698ae6c94bed862346f3af352c38

Quelldatensatz

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08314233B2