Ethanol → Ethyl 3-chloro-5-(trifluoromethyl)pyridine-2-carboxylate

Temperature

80 °C

The reaction was carried out in a 100 ml stainless steel autoclave equipped with a magnetic stirring bar. The reagents were charged in a teflon liner in the following order: (1) ethanol (20 ml), (2) sodium acetate (1.70 g, 20 mmol), (3) 2,3-dichloro-5-trifluoromethylpyridine (2.16 g [97 percent], 10 mmol), (4)1,1′-bis(diphenylphosphino)ferrocene (166 mg, 0.30 mmol [3 mol percent]), and (5) palladium acetate (12 mg, 0.05 mmol [0.5 mol percent]). The air in the autoclave was replaced with carbon monoxide and the pressure adjusted to 15 bar. The reaction mixture was then heated to 80° C. (jacket temperature) and the reaction was carried out with stirring. After 5 hours, the reaction mixture was cooled to room temperature, filtered through celite, GC analysis indicated that the mixture consisted of 98 percent of ethyl 5-trifluoromethyl-3-chloropyridine-2-carboxylate. The mixture was concentrated under vacuum and the product was isolated by flash chromatography on silica gel eluting with ethyl acetate/hexane (1:4) affording 2.34 g (92 percent, <99 percent GC area percent). Other data concerning the product was:

1. customequipped with a magnetic stirring bar
2. temperaturethe reaction mixture was cooled to room temperature
3. filtrationfiltered through celite, GC analysis
4. concentrationThe mixture was concentrated under vacuum
5. customthe product was isolated by flash chromatography on silica gel eluting with ethyl acetate/hexane (1:4)
6. customaffording 2.34 g (92 percent, <99 percent GC area percent)

ORD record

ord-b9dfb5bfc8974418946af3ee8b54b4f3

Source dataset

uspto-grants-2001_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06169183A