反应详情

Magnesium chloride (21.30 g, 224 mmol) and triethylamine (62 ml, 446 mmol) were sequentially added to a suspension of 2-tert-butoxycarbonylamidomalonic acid monoethyl ester (50.30 g, 203 mmol) in acetonitrile (300 ml) under Ar atmosphere while ice-cooled and the mixture was stirred for 1 hour. Subsequently, a solution of 6-bromopyridine-2-carbonyl chloride (37.40 g, 170 mmol) in acetonitrile (150 ml) was added dropwise at the same temperature for 3 hours, and the mixture was stirred for 1 hour. After the reaction solution was concentrated, ethyl acetate (300 ml) was added and insolubles were filtrated. The filtrate was washed with 10% aqueous citric acid, a saturated brine and dried over magnesium sulfate and an oily substance was obtained after vacuum concentration. Concentrated hydrochloric acid (200 ml) was added to an ethanol (200 ml) solution of the obtained oily substance and heated at reflux for 6 hours. After concentrated to driness under reduced pressure, the residue was washed with a mixed solvent of ethanol-isopropyl ether (1:3), collected by filtration, dried in vacuo and the title compound (25.40 g, 50%) was obtained.

1. temperaturecooled
2. stirringthe mixture was stirred for 1 hour
3. concentrationAfter the reaction solution was concentrated
4. additionethyl acetate (300 ml) was added
5. filtrationinsolubles were filtrated
6. washThe filtrate was washed with 10% aqueous citric acid
7. dry with materiala saturated brine and dried over magnesium sulfate
8. customan oily substance was obtained
9. concentrationafter vacuum concentration
10. additionConcentrated hydrochloric acid (200 ml) was added to an ethanol (200 ml) solution of the obtained oily substance
11. temperatureheated
12. temperatureat reflux for 6 hours
13. concentrationAfter concentrated to driness under reduced pressure
14. washthe residue was washed with a mixed solvent of ethanol-isopropyl ether (1:3)
15. filtrationcollected by filtration
16. customdried in vacuo