Potassium Carbonate → 2-Pyrazinecarboxylic acid, 5-(difluoromethoxy)-, methyl ester

Temperature

100 °C

To a solution of methyl 5-hydroxypyrazine-2-carboxylate (9.25 g, 60.0 mmol) in N,N-dimethylformamide (120 mL) were added potassium carbonate (24.8 g, 179 mmol) and sodium chloro(difluoro)acetate (18.3 g, 120 mmol). The mixture was heated to 100° C. for 15 minutes, whereupon it was filtered, and the filter cake was washed with ethyl acetate (2×50 mL). The combined filtrates were poured into saturated aqueous ammonium chloride solution (200 mL) and extracted with ethyl acetate (3×200 mL); the combined organic layers were washed sequentially with saturated aqueous sodium bicarbonate solution (2×300 mL) and with saturated aqueous sodium chloride solution (2×300 mL), dried, filtered, and concentrated in vacuo. Chromatography on silica gel (Gradient: 0% to 15% ethyl acetate in petroleum ether) afforded the product as a yellow solid. Yield: 1.7 g, 8.3 mmol, 14%. 1H NMR (400 MHz, CDCl3) δ 8.92 (d, J=1.2 Hz, 1H), 8.47 (d, J=1.2 Hz, 1H), 7.49 (t, JHF=71.3 Hz, 1H), 4.04 (s, 3H).

1. filtrationwas filtered
2. washthe filter cake was washed with ethyl acetate (2×50 mL)
3. additionThe combined filtrates were poured into saturated aqueous ammonium chloride solution (200 mL)
4. extractionextracted with ethyl acetate (3×200 mL)
5. washthe combined organic layers were washed sequentially with saturated aqueous sodium bicarbonate solution (2×300 mL) and with saturated aqueous sodium chloride solution (2×300 mL)
6. customdried
7. filtrationfiltered
8. concentrationconcentrated in vacuo

ORD record

ord-bd32afd15e0c4974a78e41a386751ea4

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09428523B2