6-Bromoquinoline → (Quinolin-6-yl)acetonitrile

To a mixture of (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (6.7 g, 12 mmol), tris(dibenzylideneacetone)dipalladium(0) (10 g, 12 mmol), 6-bromoquinoline (120 g, 577 mmol) in N,N-dimethylformamide (360 mL) in a 3-neck round bottom flask with stirring under positive nitrogen pressure was added (trimethylsilyl)acetonitrile (98.7 mL, 721 mmol), followed by zinc difluoride (42 g, 400 mmol). The flask was sealed under an atmosphere of nitrogen. The reaction mixture was stirred at 105° C. for 20 h. After cooling the solution to RT, the reaction mixture was quenched with an aqueous ammonia solution and extracted with ethyl acetate (3×500 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified under flash chromatography eluting with ethyl acetate in hexanes (0-65%) to afford the desired product. (70 g, 72.1%) LCMS: (M+H)=168.9.

1. customThe flask was sealed under an atmosphere of nitrogen
2. stirringThe reaction mixture was stirred at 105° C. for 20 h
3. customthe reaction mixture was quenched with an aqueous ammonia solution
4. extractionextracted with ethyl acetate (3×500 mL)
5. washThe combined organic extracts were washed with brine
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified under flash chromatography
10. washeluting with ethyl acetate in hexanes (0-65%)

ORD record

ord-b522493b9eaf49899493fe9ea68b0b38

Source dataset

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07767675B2