Hydrochloric Acid → HCID 86665041, compound

To a suspension of 5-bromo-2-chloropyridine-3-carboxylic acid (Intermediate 11, 7.0 g, 29.7 mmol) in anhydrous tetrahydrofuran (70 mL), 1,1′-carbonylbis(1H-imidazole) (CDI) (5.8 g, 35.7 mmol) was added. The reaction mixture was heated to reflux for 2 h then cooled to room temperature and the crude solution was used in the next step with out further purification. A solution of 3-ethoxy-3-oxopropanoic acid (3.93 g, 29.7 mmol) in anhydrous tetrahydrofuran (80 mL) was cooled to 0° C. and methyl magnesium bromide in diethyl ether (16 mL, 3M solution) was added in drop wise manner. After stirring for 20 min at 0° C., the crude solution which was prepared from Intermediate 11 and CDI was added and the reaction was heated to 60° C. After heating for 16 h, the reaction mixture was cooled to room temperature and then poured into water. The pH was adjusted to 5 with concentrated hydrochloric acid solution, and the solution was extracted with ethyl acetate. The organic layer was dried with anhydrous sodium sulphate and concentrated under reduce pressure to afford ethyl 3-(5-bromo-2-chloropyridin-3-yl)-3-oxopropanoate (5.0 g, 55%) as a reddish oil.

1. additionwas added
2. temperatureThe reaction mixture was heated
3. temperatureto reflux for 2 h
4. customthe crude solution was used in the next step with out further purification
5. additionwas added
6. temperaturethe reaction was heated to 60° C
7. temperatureAfter heating for 16 h
8. temperaturethe reaction mixture was cooled to room temperature
9. extractionthe solution was extracted with ethyl acetate
10. dry with materialThe organic layer was dried with anhydrous sodium sulphate
11. concentrationconcentrated

ORD record

ord-e0741fe387e3424b88d20df80d4eed68

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08569484B2