2-[(3-Bromo-2,5-dichlorophenyl)oxy]-1-chloro-3-fluoro-4-methylbenzene → 2,5-Dichloro-3-[(6-chloro-2-fluoro-3-methylphenyl)oxy]benzonitrile

HRID 1874893Notes

Reaction equation

Br[C:2]1[C:3]([Cl:19])=[C:4]([O:9][C:10]2[C:15]([F:16])=[C:14]([CH3:17])[CH:13]=[CH:12][C:11]=2[Cl:18])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[C:20]([Zn]C#N)#[N:21]>CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:19][C:3]1[C:4]([O:9][C:10]2[C:11]([Cl:18])=[CH:12][CH:13]=[C:14]([CH3:17])[C:15]=2[F:16])=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=1[C:20]#[N:21]

Participants

Conditions

Temperature: 120 °C

Procedure

2-[(3-bromo-2,5-dichlorophenyl)oxy]-1-chloro-3-fluoro-4-methylbenzene (2.0 g, 5.20 mmol) was combined with dicyanozinc (0.305 g, 2.60 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.601 g, 0.520 mmol) and heated at 120° C. for 60 min in a microwave reactor under an inert atmosphere. The reaction mixture was diluted with EtOAc, washed four times with water, dried over MgSO4, filtered and concentrated to dryness. The residue was purified on 120 g silica eluted successively with 100% hexanes followed by 0 to 10% EtOAc/hexanes to give 2,5-dichloro-3-[(6-chloro-2-fluoro-3-methylphenyl)oxy]benzonitrile (1.01 g, 3.06 mmol, 58.7% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.00 (d, J=2.20 Hz, 1H), 7.31-7.47 (m, 2H), 7.24 (d, J=1.83 Hz, 1H), 2.29 (d, J=1.74 Hz, 3H).

Workup

washwashed four times with water
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated to dryness
customThe residue was purified on 120 g silica
washeluted successively with 100% hexanes

Sources & evidence

ORD record: ord-f54c6704b06342e9827deca19e35d9e7
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08304419B2

Reaction notes

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