Sodium Carbonate → 7-Fluoroquinoline-6-carbonitrile

HRID 449251Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[N:8]=[CH:7][CH:6]=[CH:5]2.C(=O)([O-])[O-].[Na+].[Na+].C[C:20]([N:22](C)C)=O>[Fe-4](C#N)(C#N)(C#N)(C#N)(C#N)C#N.[K+].[K+].[K+].[K+].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:12][C:11]1[CH:10]=[C:9]2[C:4]([CH:5]=[CH:6][CH:7]=[N:8]2)=[CH:3][C:2]=1[C:20]#[N:22]

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of 6-bromo-7-fluoroquinoline (4.90 g, 22.12 mmol) in dimethylacetamide (38 ml), potassium ferrocyanide (2.65 g, 4.86 mmol) and sodium carbonate (2.34 g, 22.12 mmol). The system was purged with nitrogen for 15 min. Palladium acetate (0.248 g, 1.10 mmol) was added under nitrogen and heated to 120° C. After 3 h, the reaction mixture was filtered through celite, washed with ethyl acetate. The organic layer was washed with brine solution, dried over sodium sulphate and concentrated. The crude product was purified by column chromatography with ethyl acetate: petroleum ether to afford the title compound as a white solid (3.2 g, 86%). 1H-NMR (δ ppm, CDCl3, 400 MHz): 9.05 (dd, J=4.1, 2.9 Hz, 1H), 8.25 (m, 2H), 7.90 (d, J=10.0 Hz, 1H), 7.53 (dd, J=8.3, 4.3 Hz, 1H).

Workup

customThe system was purged with nitrogen for 15 min
filtrationthe reaction mixture was filtered through celite
washwashed with ethyl acetate
washThe organic layer was washed with brine solution
dry with materialdried over sodium sulphate
concentrationconcentrated
customThe crude product was purified by column chromatography with ethyl acetate

Sources & evidence

ORD record: ord-a5a2d1b955be47479e6218c993e91da6
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08481739B2

Reaction notes

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