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

Temperatur

-30 °C

Ethyl 3-piperidin-1-ylacrylate (94%, 9.4 g, 48 mmol) was initially charged in toluene (100 ml) and cooled to −30° C. At this temperature, difluoroacetyl fluoride (5.0 g, 51 mmol) was introduced. Tributylamine (9.5 g, 51 mmol) was then added to the reaction mixture. 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 (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: 12.7 g; purity according to GC: 82.15%; yield: 82.8%).

1. waitover a period of 1 hour
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-Eintrag

ord-0a880231a3c04e92b2c01f5c1343fd68

Quelldatensatz

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08314233B2