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

Temperature

-30 °C

Methyl 3-piperidin-1-ylacrylate (99%, 26.6 g, 155 mmol) and triethylamine (17.3 g, 171 mmol) were initially charged in toluene (300 ml) and cooled to −30° C. At this temperature, difluoroacetyl chloride (20 g, 171 mmol) was introduced. The reaction mixture was stirred at −30° C. for 3 h, another 200 ml of toluene were added to keep the suspension stirrable and the mixture was then warmed to room temperature over a period of 1 hour. 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: 37.6 g; purity according to quant. NMR: 82.2%; yield: 80.3%).

1. temperaturethe mixture was then warmed to room temperature over a period of 1 hour
2. washThe reaction mixture was washed with deionized water (200 ml)
3. customAfter separation of the phases
4. extractionthe aqueous phase was extracted once with toluene (100 ml)
5. washwashed with an aqueous saturated NaCl solution (100 ml)
6. customthe solvent was then removed under reduced pressure

ORD record

ord-233cc7eb43d249aca61e4a7f0fcf487e

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08314233B2