Trifluoroacetic anhydride → ethyl 2-[(E)-2-phenylethenyl]-1,3-oxazole-4-carboxylate

Temperature

0 °C

A mixture of (2E)-3-phenylprop-2-enamide (2.00 g, 13.6 mmol) and sodium bicarbonate (4.57 g, 54.4 mmol) in tetrahydrofuran (48 mL) was cooled to 0° C. Ethyl 3-bromo-2-oxopropanoate (3.16 mL, 25.2 mmol) was added drop-wise, and the reaction mixture was heated at reflux for 4 hours, whereupon it was filtered through diatomaceous earth and concentrated in vacuo. The residue was dissolved in tetrahydrofuran (33 mL), cooled to 0° C., and treated drop-wise with trifluoroacetic anhydride (14.8 mL, 105 mmol). The reaction mixture was stirred at room temperature for 10 hours, then cooled to 0° C. and quenched via addition of saturated aqueous sodium bicarbonate solution. The mixture was extracted three times with ethyl acetate, and the combined organic layers were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Chromatography on silica gel (Gradient: 0% to 30% ethyl acetate in heptane) provided partially purified product; this was crystallized from heptane/ethyl acetate to afford the product as pale yellow needles. Yield: 1.52 g, 6.25 mmol, 46%. LCMS m/z 244.1 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 8.20 (s, 1H), 7.63 (d, J=16.4 Hz, 1H), 7.51-7.56 (m, 2H), 7.34-7.43 (m, 3H), 6.97 (d, J=16.5 Hz, 1H), 4.42 (q, J=7.1 Hz, 2H), 1.41 (t, J=7.1 Hz, 3H).

1. temperaturethe reaction mixture was heated
2. temperatureat reflux for 4 hours, whereupon it
3. filtrationwas filtered through diatomaceous earth
4. concentrationconcentrated in vacuo
5. dissolutionThe residue was dissolved in tetrahydrofuran (33 mL)
6. temperaturecooled to 0° C.
7. temperaturecooled to 0° C.
8. customquenched via addition of saturated aqueous sodium bicarbonate solution
9. extractionThe mixture was extracted three times with ethyl acetate
10. washthe combined organic layers were washed with saturated aqueous sodium chloride solution
11. dry with materialdried over sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated under reduced pressure
14. customChromatography on silica gel (Gradient: 0% to 30% ethyl acetate in heptane) provided partially purified product
15. customthis was crystallized from heptane/ethyl acetate

ORD record

ord-cc82f2f516724d309a80738751d02d56

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09315520B2