3-(3-Bromo-4-fluorophenyl)-3-methylbutan-2-one → 2-Fluoro-5-(2-methyl-3-oxobutan-2-yl)benzonitrile

HRID 1627366Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([C:9]([CH3:14])([CH3:13])[C:10](=[O:12])[CH3:11])[CH:5]=[CH:6][C:7]=1[F:8].[C:15]([Cu])#[N:16]>CN1C(=O)CCC1.CCOC(C)=O>[F:8][C:7]1[CH:6]=[CH:5][C:4]([C:9]([CH3:14])([C:10](=[O:12])[CH3:11])[CH3:13])=[CH:3][C:2]=1[C:15]#[N:16]

Participants

Conditions

Temperature: 160 °C

Procedure

To a solution of 3-(3-bromo-4-fluorophenyl)-3-methylbutan-2-one (13 g, 50 mmol) in NMP (100 mL) was added CuCN (17.9 g, 200 mmol, 4 eq). The mixture was heated 24 h at 160° C. After cooling, the reaction was diluted with EtOAc, washed with 2N HCl (200 mL), satd NaHCO3 (200 mL) and brine (200 mL) successively, dried over MgSO4 and evaporated in vacuo. The residue was purified by column chromatography (Hex/EtOAc=4:1) to give 2-fluoro-5-(2-methyl-3-oxobutan-2-yl)benzonitrile (7.1 g, 69%). 1H NMR (400 MHz, CDCl3) δ 7.56-7.54 (m, 1H), 7.49-7.45 (m, 1H), 7.20 (t, J=8.4 Hz, 1H), 1.96 (s, 3H), 1.50 (s, 6H).

Workup

temperatureAfter cooling
washwashed with 2N HCl (200 mL), satd NaHCO3 (200 mL) and brine (200 mL) successively
dry with materialdried over MgSO4
customevaporated in vacuo
customThe residue was purified by column chromatography (Hex/EtOAc=4:1)

Sources & evidence

ORD record: ord-2f36a35aaf084f03b95342fee5c95d4f
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08785488B2

Reaction notes

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