Hydrochloric Acid → 7-Cyano-1,2,3,4-tetrahydroisoquinoline

Temperature

-5 °C

Hydrochloric acid (30.6 ml; 2 equiv.) was added at 0° C. to a solution of 1,2,3,4,-tetrahydroisoquinoline-7-amine (15.3 g; 1 equiv.) in 40 ml of water, and the reaction mixture was stirred for 10 minutes at −5° C. Sodium nitrate solution (7.13 g of sodium nitrate in 35 ml of water) was added dropwise at 0° C. in the course of 30 minutes, and the resulting reaction mixture was stirred for 30 minutes at 0° C. Finally, urea (1.86 g; 0.3 equiv.) was added. A mixture of sodium hydroxide solution (10.3 g of NaOH in 70 ml of H2O), potassium cyanide solution (33.5 g (5 equiv.) of KCN in 50 ml of H2O) and 76.5 ml of benzene was cooled to 0° C.; a nickel sulfate solution (32.6 g (1.2 equiv.) of NiSO4*6H2O in 50 ml of H2O) was added slowly, and stirring was carried out for 30 min. at 0° C. The diazonium solution was slowly added dropwise at 0° C., and the resulting reaction mixture was stirred first for 2 h at room temperature and then for 1 h at 50° C. When the conversion was complete, the mixture was cooled to 0° C., adjusted to a pH value of 8-9 with sodium hydroxide solution and filtered over Celite, and the filter cake was then washed with dichloromethane. The aqueous solution was extracted 3 times with dichloromethane. The combined organic phases were dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel, 10% methanol/chloroform). 1,2,3,4-Tetrahydroisoquinoline-7-carbonitrile (4 g; 24.5%) was obtained in the form of a solid.

1. customthe resulting reaction mixture
2. stirringwas stirred for 30 minutes at 0° C
3. temperaturewas cooled to 0° C.
4. stirringstirring
5. waitwas carried out for 30 min. at 0° C
6. customthe resulting reaction mixture
7. stirringwas stirred first for 2 h at room temperature
8. waitfor 1 h at 50° C
9. temperaturethe mixture was cooled to 0° C.
10. filtrationfiltered over Celite
11. washthe filter cake was then washed with dichloromethane
12. extractionThe aqueous solution was extracted 3 times with dichloromethane
13. dry with materialThe combined organic phases were dried over sodium sulfate
14. concentrationconcentrated under reduced pressure
15. customThe crude product was purified by column chromatography (silica gel, 10% methanol/chloroform)

ORD record

ord-40a75724559041ce88fa0aef936066d5

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08357717B2