3-Bromo-4-fluorobenzoyl chloride → 2-(3-Bromo-4-fluoro-benzoyl)-6-fluoro-benzonitrile

HRID 1662175Notes

Reaction equation

[C:1]([C:3]1[C:8]([F:9])=[CH:7][CH:6]=[CH:5][C:4]=1[Zn])#[N:2].[Br:11][C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][C:20]=1[F:21])[C:15](Cl)=[O:16]>C1COCC1>[Br:11][C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][C:20]=1[F:21])[C:15]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]([F:9])[C:3]=1[C:1]#[N:2])=[O:16]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 2-cyano-3-fluorophenylzinc (80.0 mL, 40.0 mmol, 0.5 M in THF), tetrakistriphenylphosphine palladium(0) (2.3 g, 2.0 mmol) was added in small portions at 0° C. A solution of 3-bromo-4-fluorobenzoyl chloride (10.0 g, 42.1 mmol) in anhydrous THF (20 mL) was then added dropwise and the reaction mixture was stirred at 0° C. for 1 hour. The reaction was quenched by addition of water (150 mL) and the resulting mixture was extracted with ethyl acetate (2×150 mL). The combined organic extracts were washed with brine, dried over sodium sulfate and concentrated in vacuo. The crude product was purified by flash column chromatography using 30% ethyl acetate in hexanes to afford the title compound (7.90 g, 61% yield).

Workup

customThe reaction was quenched by addition of water (150 mL)
extractionthe resulting mixture was extracted with ethyl acetate (2×150 mL)
washThe combined organic extracts were washed with brine
dry with materialdried over sodium sulfate
concentrationconcentrated in vacuo
customThe crude product was purified by flash column chromatography

Sources & evidence

ORD record: ord-fbfa14684eed4c709d5c57fd0b6b9c84
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08030500B2

Reaction notes

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