Sodium Carbonate → 7-Fluoroquinoline-6-carbonitrile

HRID 1404770Notes

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-c33e91b794874681a4d4d597d6914fb3
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08912331B2

Reaction notes

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