Cesium carbonate → Methyl 5-(2,2,2-trifluoroethoxy)pyridine-2-carboxylate

Methyl 5-hydroxypyridine-2-carboxylate (Intermediate 224, 0.610 g, 3.59 mmol) was dissolved in DMF (5 mL), cesium carbonate (1.40 g, 4.31 mmol) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (1.0 g, 4.31 mmol) were added and the mixture stirred at room temperature for 18 h. The mixture was partitioned between EtOAc (50 mL) and water (15 mL) and the aqueous layer extracted with further EtOAc (2×20 mL). The combined organic layers were dried over sodium sulfate and concentrated under vacuum. The crude material was purified by FCC, eluting with a gradient of 0-50% EtOAc in heptane to afford the title compound as a white solid (0.652 g, 77%). 1H NMR (500 MHZ, CDCl3) δ ppm 8.40 (1H, d), 8.09 (1H, d), 7.27 (1H, dd), 4.41 (2H, q) and 3.93 (3H, s).

1. customThe mixture was partitioned between EtOAc (50 mL) and water (15 mL)
2. extractionthe aqueous layer extracted with further EtOAc (2×20 mL)
3. dry with materialThe combined organic layers were dried over sodium sulfate
4. concentrationconcentrated under vacuum
5. customThe crude material was purified by FCC
6. washeluting with a gradient of 0-50% EtOAc in heptane

ORD record

ord-35906ed04eb943f8b5a572a40bf2792a

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08895733B2