Dimethylformamide → 5-Bromoquinoline-8-carbonitrile

HRID 523960Notes

Reaction equation

[Br:1][C:2]1[CH:11]=[CH:10][C:9](I)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.[CH3:13][N:14](C=O)C>O.[C-]#N.[C-]#N.[Zn+2].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Br:1][C:2]1[CH:11]=[CH:10][C:9]([C:13]#[N:14])=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2

Participants

Conditions

Temperature: 95 °C

Procedure

A mixture of 5-bromo-8-iodoquinoline (0.52 g, 1.55 mmol), Zn(CN)2 (218 mg, 1.86 mmol), and dppf (103 mg, 0.186 mmol) in DMF (2.5 mL) was purged with N2 (gas) for 5 minutes. Pd2(dba)3 (85 mg, 0.093 mmol) was added and the resulting mixture was heated at 95° C. for 5 h. After completion of the reaction, it was cooled to r.t., diluted with water, and the aqueous solution was extracted with ethyl acetate (3×50 mL). The combined organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel, eluting with ethyl acetate-hexanes (5-25%) to get 5-bromoquinoline-8-carbonitrile as a brown solid (72 mg).

Workup

customwas purged with N2 (gas) for 5 minutes
customAfter completion of the reaction, it
temperaturewas cooled to r.t.
extractionthe aqueous solution was extracted with ethyl acetate (3×50 mL)
washThe combined organic layer was washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated under reduced pressure
customThe crude product was purified by column chromatography on silica gel
washeluting with ethyl acetate-hexanes (5-25%)

Sources & evidence

ORD record: ord-e4ef009439124ea6a71cf149fa0562a7
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09340509B2

Reaction notes

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