反应详情

温度

120 °C

Zinc cyanide (744 mg), potassium hydroxide (470 mg) and tetrakis(triphenylphosphine)palladium (0) (1.82 g) were sequentially added to a solution of 1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl trifluoromethanesulfonate (1.55 g) in NMP (15 ml), followed by stirring at 120° C. for 3 hours. Chloroform was added to the reaction solution, the precipitated solid was separated by filtration, and the solvent of the filtrate was evaporated. The residue was purified by silica gel chromatography (hexane:ethyl acetate=100:0 to 0:100), and the solvent was evaporated under reduced pressure. Subsequently, ethylene glycol (10 ml) and 3M aqueous sodium hydroxide solution (30 ml) were added to the resulting residue, followed by stirring at 100° C. for 3 hours. After cooling to room temperature, water was added thereto, followed by extraction with diethylether. Concentrated hydrochloric acid was added to the aqueous layer, the pH was adjusted to 2 to 3, ethyl acetate was added for re-extraction, the organic layer was washed with saturated brine, and the solvent was evaporated under reduced pressure. Ethyl acetate was added, and the solid was precipitated, filtered and dried under vacuum to obtain, as a colorless solid, 1-oxo-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid (324 mg).

1. customthe precipitated solid was separated by filtration
2. customthe solvent of the filtrate was evaporated
3. customThe residue was purified by silica gel chromatography (hexane:ethyl acetate=100:0 to 0:100)
4. customthe solvent was evaporated under reduced pressure
5. additionSubsequently, ethylene glycol (10 ml) and 3M aqueous sodium hydroxide solution (30 ml) were added to the resulting residue
6. stirringby stirring at 100° C. for 3 hours
7. temperatureAfter cooling to room temperature
8. additionwater was added
9. extractionfollowed by extraction with diethylether
10. additionConcentrated hydrochloric acid was added to the aqueous layer
11. additionwas added for re-extraction
12. washthe organic layer was washed with saturated brine
13. customthe solvent was evaporated under reduced pressure
14. additionEthyl acetate was added
15. customthe solid was precipitated
16. filtrationfiltered
17. customdried under vacuum