4-Bromoisoquinoline → 4-Fluoroisoquinoline

A solution of n-butyllithium in n-hexane (1.58 M, 60.1 ml, Kanto Chemicals) was added with tetrahydrofuran (345 ml), and the mixture was sufficiently cooled on a dry ice-acetone bath. The mixture was added dropwise with a solution of 4-bromoisoquinoline (9.0 g, Tokyo Kasei Kogyo) in tetrahydrofuran (65 ml) over 1 hour so that the temperature of the reaction mixture should not exceed −65° C. The mixture was stirred at the same temperature for 30 minutes, and then added dropwise with a solution of N-fluorobenzenesulfonimide (30 g, Tokyo Kasei Kogyo) in tetrahydrofuran (100 ml) over 1 hour so that the temperature of the reaction mixture should not exceed −65° C. Subsequently, the mixture was stirred at the same temperature for 1 hour, then the cooling bath was removed, and the mixture was gradually warmed to room temperature. The reaction mixture was added with saturated aqueous sodium hydrogencarbonate (300 ml) and ethyl acetate (300 ml), and stirred at room temperature for 12 hours. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate 3 times (200 ml for each time). The combined organic layer was washed with saturated brine (500 ml), and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, the residue was added with chloroform (250 ml), and the insoluble solids were removed by filtration. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography (n-hexane:ethyl acetate=5:1) to obtain the title compound (3.6 g).

1. temperaturethe mixture was sufficiently cooled on a dry ice-acetone bath
2. customexceed −65° C
3. customexceed −65° C
4. stirringSubsequently, the mixture was stirred at the same temperature for 1 hour
5. customthe cooling bath was removed
6. additionThe reaction mixture was added with saturated aqueous sodium hydrogencarbonate (300 ml) and ethyl acetate (300 ml)
7. stirringstirred at room temperature for 12 hours
8. customThe organic layer was separated
9. extractionthe aqueous layer was extracted with ethyl acetate 3 times (200 ml for each time)
10. washThe combined organic layer was washed with saturated brine (500 ml)
11. dry with materialdried over anhydrous magnesium sulfate
12. customThe solvent was evaporated under reduced pressure
13. additionthe residue was added with chloroform (250 ml)
14. customthe insoluble solids were removed by filtration
15. customThe solvent was evaporated under reduced pressure
16. customthe residue was purified by silica gel chromatography (n-hexane:ethyl acetate=5:1)

ORD-Eintrag

ord-8f6fd553fbe44b20b5a6b565cea8f75a

Quelldatensatz

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07964613B2