Diethyl Carbonate → Ethyl 2-(6-chloropyridin-2-yl)acetate

Temperature

-70 °C

n-Butyl lithium (23% in hexane, 13.2 mL, 47.3 mmol) was added dropwise to a cold solution (−70° C.) of 2-chloro-6-methyl-pyridine (5.0 g, 39.4 mmol) in tetrahydrofuran (30 mL) and stirred for 30 min at −70° C. Diethyl carbonate (5.75 mL, 47.3 mmol) was added slowly and the reaction mixture stirred for 30 min at −70° C. before warning to room temperature and stirring for a further 1 h. The reaction mixture was quenched into saturated ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with water and brine, then dried over sodium sulfate, filtered and concentrated to yield the crude compound which was purified by column chromatography over silica gel (100-200 mesh), using 9% ethyl acetate in petroleum ether as eluent, to afford (6-chloro-pyridin-2-yl)-acetic acid ethyl ester (2.21 g, 28%) as an oil.

1. stirringthe reaction mixture stirred for 30 min at −70° C.
2. custombefore warning to room temperature
3. stirringstirring for a further 1 h
4. customThe reaction mixture was quenched into saturated ammonium chloride solution
5. extractionextracted with ethyl acetate
6. washThe organic layer was washed with water and brine
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customto yield the crude compound which
11. customwas purified by column chromatography over silica gel (100-200 mesh)

ORD record

ord-bbe2038d7f0a4137bd1b3ddcaac393e5

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08604029B2