反应详情

A mixture of 4-chloro-5-fluoro-nicotinonitrile (3.5 g, 22.4 mmol), glycine ethyl ester hydrochloride (9.4 g, 67.1 mmol) and sodium hydrogencarbonate (11.3 g, 134.2 mmol) in IMS (60 mL) was stirred at reflux for 18 hours. The reaction was then cooled to room temperature and partitioned between water and ethyl acetate. The organic layer was separated and washed with water and brine, dried over sodium sulphate, filtered and concentrated to give a solid which was triturated in diethyl ether. The mixture was aged at room temperature for 18 hours and the precipitate was filtered off and dried under vacuum at 60° C. to give the title compound as a beige solid (2.29 g, 46%). LCMS (method B): RT=1.50 min, M+H+=224.

1. temperatureat reflux for 18 hours
2. custompartitioned between water and ethyl acetate
3. customThe organic layer was separated
4. washwashed with water and brine
5. dry with materialdried over sodium sulphate
6. filtrationfiltered
7. concentrationconcentrated
8. customto give a solid which
9. customwas triturated in diethyl ether
10. filtrationthe precipitate was filtered off
11. customdried under vacuum at 60° C.