Cesium carbonate → Ethyl 2-((5-chloro-2-cyanopyridin-3-yl)oxy)acetate

To a mixture of cesium carbonate (1.63 g, 5.01 mmol) and 5-chloro-3-fluoropicolinonitrile (0.784 g, 5.01 mmol) was added NMP (5 mL) and ethyl glycolate (0.52 mL, 5.49 mmol). The reaction mixture was stirred at RT for 20 min, heated to 80° C. for 1 h and additional ethyl glycolate (0.10 mL) was added. Stirring was continued at 80° C. for 2 h and the reaction mixture was cooled to RT. The reaction was and diluted with EtOAc and water. The aqueous phase was extracted with EtOAc (2×) and the combined organic extracts were washed with brine (1×), dried over MgSO4, filtered, and concentrated. Purification by flash column chromatography on silica gel eluting with a gradient of 0% to 15% EtOAc in DCM gave ethyl 2-((5-chloro-2-cyanopyridin-3-yl)oxy)acetate (0.83 g, 3.46 mmol, 69% yield) as a white solid. LC/MS (ESI+) m/z=240.9 (M+H). Calculated for C10H9ClN2O3 240.0.

1. temperatureheated to 80° C. for 1 h
2. stirringStirring
3. waitwas continued at 80° C. for 2 h
4. temperaturethe reaction mixture was cooled to RT
5. extractionThe aqueous phase was extracted with EtOAc (2×)
6. washthe combined organic extracts were washed with brine (1×)
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. customPurification by flash column chromatography on silica gel eluting with a gradient of 0% to 15% EtOAc in DCM

ORD record

ord-ce5db13f9bcf409b9522ce122b2ef8dd

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09085576B2