4-Bromo-2-fluorophenol → 3'-Fluoro-4'-hydroxy[1,1'-biphenyl]-4-carbonitrile

HRID 1167858Notes

Reaction equation

[C:1]([C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1)#[N:2].Br[C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[C:15]([F:20])[CH:14]=1.O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC(O)C.O>[F:20][C:15]1[CH:14]=[C:13]([C:6]2[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][CH:5]=2)[CH:18]=[CH:17][C:16]=1[OH:19]

Participants

Conditions

Temperature: 70 °C

Procedure

4-Cyanophenylboronic acid (0.92 g, 6.26 mmol), 4-bromo-2-fluorophenol (1.0 g, 5.2 mmol), potassium phosphate tribasic monohydrate (3.0 g, 15.6 mmol) and Pd (Ph3P)2Cl2 (73.0 mg, 0.1 mmol) were combined in a mixture of IPA/H2O (40 mL, 3:1) and heated at 70° C. After 2 hours, the mixture was allowed to cool to room temperature and was filtered over celite. The filtrate was diluted with 150 ml of CH2Cl2 and washed with water twice. The organic phase was dried over sodium sulfate, filtered, and the filtrate concentrated under reduced pressure. The residue was chromatographed over silica gel using CH2Cl2 to provide the title compound as a white powder (0.61 g, 55% yield). 1HNMR (300 MHz, CDCl3) δ5.20 (bs, 1H), 7.15-7.78 (m, 7H); MS (DCI) m/z 214 (M+H)+.

Workup

temperatureto cool to room temperature
filtrationwas filtered over celite
additionThe filtrate was diluted with 150 ml of CH2Cl2
washwashed with water twice
dry with materialThe organic phase was dried over sodium sulfate
filtrationfiltered
concentrationthe filtrate concentrated under reduced pressure
customThe residue was chromatographed over silica gel

Sources & evidence

ORD record: ord-50676dfa89ad41b2bcc41fb8b6c0490f
Source dataset: uspto-grants-2003_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06620839B2

Reaction notes

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