Diisopropylamine → HCID 22406838, compound

Temperature

0 °C

n-Butyl lithium (24.5 ml, 2M solution in hexane) was added to a solution of diisopropylamine (6.85 ml) in tetrahydrofuran (50 ml) at 0° C. The resulting solution of lithium diisopropylamide was stirred at 0° C. for 20 minutes. A solution of 1-cyclobutyl-3,4-dihydro-6,7-dimethoxyisoquinoline (10 g) in tetrahydrofuran (100 ml) was added. The mixture was stirred at 0° C. for 1 hour, then cooled to -70° C. and treated dropwise with 2-fluorobenzonitrile (4.42 ml). The mixture was stirred at -70° C. for 50 minutes, then allowed to warm slowly to ambient temperature. The mixture was poured onto hydrochloric acid and washed with ether. The aqueous phase was basified with ammonia solution and the product was extracted with ethyl acetate. The resulting solid (0.6 g) was collected by filtration. The filtrate was washed with brine, dried over magnesium sulphate and the solvent removed in vacuo to give further solid. The combined solids were recrystallised from acetonitrile yielding a solid which was dried in vacuo to give 1-[1-(2-cyanophenyl)cyclobutyl]-6,7-dimethoxy-3,4-dihydroisoquinoline (5 g).

1. temperaturecooled to -70° C.
2. stirringThe mixture was stirred at -70° C. for 50 minutes
3. temperatureto warm slowly to ambient temperature
4. additionThe mixture was poured onto hydrochloric acid
5. washwashed with ether
6. extractionthe product was extracted with ethyl acetate
7. filtrationThe resulting solid (0.6 g) was collected by filtration
8. washThe filtrate was washed with brine
9. dry with materialdried over magnesium sulphate
10. customthe solvent removed in vacuo
11. customto give further solid
12. customThe combined solids were recrystallised from acetonitrile yielding a solid which
13. customwas dried in vacuo

ORD record

ord-b3fb60038d4e4ecdb689a6211a840e78

Source dataset

uspto-grants-1996_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05519034