反应详情

To a suspension of 3-(4-trifluoromethyl-phenyl)-acrylamide (5.0 g, 23.2 mmol) and NaHCO3 (7.80 g, 92.9 mmol) in THF (90 ml) 3-bromo-2-oxo-propionic acid ethyl ester (5.53 g, 25.6 mmol) is added under an argon atmosphere. The mixture is heated to reflux for 15 h when another portion of 3-bromo-2-oxo-propionic acid ethyl ester (5.53 g, 25.6 mmol) is added and stirring continued for 5 h. After cooling to r.t. the mixture is filtered, concentrated in vacuo and the resulting residue suspended in THF (20 ml). At 0° C. trifluoroacetic acid anhydride (16.3 g, 77.9 mmol) is added and the mixture stirred at room temperature for 16 h. The mixture is neutralized with sat. NaHCO3, the aqueous layer extracted with ethyl acetate (2×200 ml) and the combined organic phases dried over Na2SO4 and concentrated in vacuo. The crude product is purified by flash column chromatography (ethyl acetate/heptane 4:1) yielding 2-[2-(4-trifluoromethyl-phenyl)-vinyl]-oxazole-4-carboxylic acid ethyl ester as a colorless solid. Yield 5.84 g (81%)

1. additionis added under an argon atmosphere
2. temperatureThe mixture is heated
3. additionis added
4. filtrationis filtered
5. concentrationconcentrated in vacuo
6. stirringthe mixture stirred at room temperature for 16 h
7. extractionthe aqueous layer extracted with ethyl acetate (2×200 ml)
8. dry with materialthe combined organic phases dried over Na2SO4
9. concentrationconcentrated in vacuo
10. customThe crude product is purified by flash column chromatography (ethyl acetate/heptane 4:1)